Updated on 2024/10/31

Information

 

写真a

 
MASUDA TAKAHIRO
 
Organization
Medical Institute of Bioregulation Medical Research Center for High Depth Omics Professor
Graduate School of Medical Sciences Department of Medical Sciences（Concurrent）
Graduate School of Medical Sciences Department of Medicine（Concurrent）
Title
Professor
Contact information
メールアドレス
Homepage
External link

Research Areas

  • Life Science / Pharmacology

  • Life Science / Neuroscience-general

  • Life Science / Clinical pharmacy

  • Life Science / Immunology

Degree

  • Ph.D.

Research History

  • Kyushu University Medical Institute of Bioregulation Professor

    2023.1 - Present

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  • Kyushu University Associate Professor

    2021.6 - 2022.12

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  • 2015.5-2017.5 University of Freiburg (Germany), Visiting Scientist(日本学術振興会・海外特別研究員) 2017.6-2020.2 University of Freiburg (Germany), Postdoc

Research Interests・Research Keywords

  • Research theme：Microglia

    Keyword：Microglia

    Research period： 2024

  • Research theme：１細胞解析

    Keyword：１細胞解析

    Research period： 2024

  • Research theme：脳境界生物学

    Keyword：脳境界生物学

    Research period： 2024

  • Research theme：CNS border-associated macrophages

    Keyword：CNS border-associated macrophages

    Research period： 2024

  • Research theme：脳内免疫

    Keyword：脳内免疫

    Research period： 2024

  • Research theme：Neurodegenerative disorder

    Keyword：Neurodegenerative disorder

    Research period： 2024

  • Research theme：発生

    Keyword：発生

    Research period： 2024

  • Research theme：Understanding the nature of CNS macrophages

    Keyword：microglia, CAMs, central nervous system

    Research period： 2020.3

Awards

  • 第20回（令和５年度）日本学術振興会賞

    2023.12   日本学術振興会   脳内マクロファージの統合的理解に向けた多角的研究

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    研究業績「脳内マクロファージの統合的理解に向けた多角的研究」において、第20回日本学術振興会賞受賞者に選ばれた。

  • 2023年度日本神経化学会　優秀賞

    2023.7   日本神経化学会   脳内マクロファージの統合的理解に向けた研究

  • 第１回　石館・上野賞

    2022.11   公益財団法人　中外創薬科学財団   脳内マクロファージの統合的理解と研究基盤の創出

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    受賞者・増田は、脳内マクロファージとして知られるミクログリア細胞および脳境界マクロファージの研究に取り組み、その発生・正常分布メカニズム・多様性・生理機能および病態発症における役割に関する卓越した研究成果を上げてきた（PNAS, 2009; Cell Rep, 2012, 2020; Nature Commun, 2014, 2016; Nature, 2019, 2022; Nature Immunol, 2020; Science 2022など38報）。特に、１細胞解析等の最新技術を駆使した研究では、中枢神経系疾患特異的に出現するヒトミクログリアサブセットを世界で初めて同定した。こうした疾患治療標的の創出に直結する顕著な研究成果が高く評価され、令和3年度 科学技術部門の文部科学大臣表彰若手科学者賞を受賞しました。さらに、当該研究領域のレベルを格段に向上させる汎用性の高い細胞機能操作ツールの独自開発にも成功し、これまでの概念を覆す脳境界マクロファージの発生学的な特徴を明らかにした。今後これらの研究基盤をさらに発展させ、画期的な成果を上げることが期待される。

  • 令和３年度文部科学大臣表彰　若手科学者賞

    2021.4   文部科学省   科学技術に関する研究開発、理解増進等において顕著な成果を収めた者に授与される科学技術分野の文部科学大臣表彰 研究課題：脳内免疫細胞ミクログリアの存在意義解明に向けた包括的研究

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    近年、脳内免疫細胞であるミクログリアが、様々な中枢神経系疾患の発症に関与することが明らかになってきた。そのため、新たな創薬ターゲットとして注目されているが、その存在意義や多様性などの基盤情報、特には ヒトにおける解析データは国際的にみても乏しかった。
    増田隆博 氏は、最先端の網羅的１1 細胞解析技術等を駆使して、実験モデル動物のみならず、ヒト脳組織内におけるミクログリアの機能や多様性等に関する包括的な研究を世界に先駆けて取り組んだ。
    本研究成果は、ミクログリアの生命原理の理解に直結する重要な基盤情報であり、ミクログリアの機能的側面および多様性に関する理解を大きく前進させた。今後、ミクログリアを標的とした新規治療薬の創出が加速するものと期待される。

  • 2014年度日本神経化学会奨励賞

    2014.9   日本神経化学会   賞の内容：将来の発展を期待される若手神経化学研究者個人に対して授与する 研究課題：IRF転写因子ファミリーによる活性化ミクログリアの表現型制御

  • Best Poster Prize

    2014.7   Purine2014  

  • Poster of the day (Poster award)

    2012.6   Purine2012  

  • Poster Presentation Award

    2010.10   The 29th Naito Conference- GLIA WORLD- Dynamic function of Glial cells in the Brain  

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    Neuropathic pain occurs after several diseases accompanied by nerve damage, which is characterized by abnormal sensory perception such as tactile allodynia (nocuous response to innocuous mechanical stimuli). This debilitating pain condition arises as a consequence of excessive excitability of neurons in the spinal dorsal horn, and the neuronal hyperexcitability involves signaling from activated spinal microglia that have induced or enhanced expression of various genes including proinflammatory cytokines. However, a key transcription factor regulating gene expression and neuropathic pain states is not identified. Here we report that interferon regulatory factor-8 (IRF-8), a member of IRF family transcription factor, controls gene expression in activated microglia responsible for tactile allodynia. Peripheral nerve injury (PNI) increased the expression of IRF-8 in spinal microglia in a cell type-specific manner. Furthermore, IRF-8-deficient mice (irf8-/-) exhibited a marked reduction in allodynia after PNI compared with wild-type mice without affecting normal pain sensitivity. In contrast, these mice showed a similar pain behavior in an inflammatory chronic pain model. Interestingly, irf8-/- mice failed to increase the expression of genes crucial for producing pain hypersensitivity in the spinal cord following PNI. Together, our present findings suggest that IRF-8 is the crucial intermediary for upregulating pain-related molecules and subsequent neuropathic pain.

  • Best Poster Award

    2009.7  

  • 第８２回薬理学会年会優秀発表賞

    2009.3   日本薬理学会   Lyn tyrosine kinase is essential for interferon-γ-dependent spinal microglia activation driving neuropathic painに関する発表

  • Poster Award

    2008.7   The 3rd Asian Pain Symposium  

  • 学会奨励賞

    2007.5   Intrathecal administration of interferon-γ activates spinal microglia and causes long-lasting tactile allodynia という演題での発表で受賞

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Papers

  • IRF8 and MAFB drive distinct transcriptional machineries in different resident macrophages of the central nervous system Reviewed

    Ayato Yamasaki, Iroha Imanishi, Kaori Tanaka, Yasuyuki Ohkawa, Makoto Tsuda, Takahiro Masuda

    Communications Biology   7 ( 1 )   896   2024.7   （ eISSN:2399-3642 ）

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s42003-024-06607-6

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  • Mechanisms of myeloid cell entry to the healthy and diseased central nervous system. Reviewed International coauthorship International journal

    Lukas Amann, Takahiro Masuda, Marco Prinz

    Nature immunology   24 ( 3 )   393 - 407   2023.3   （ ISSN:1529-2908 eISSN:1529-2916 ）

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    Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    Myeloid cells in the central nervous system (CNS), such as microglia, CNS-associated macrophages (CAMs), dendritic cells and monocytes, are vital for steady-state immune homeostasis as well as the resolution of tissue damage during brain development or disease-related pathology. The complementary usage of multimodal high-throughput and high-dimensional single-cell technologies along with recent advances in cell-fate mapping has revealed remarkable myeloid cell heterogeneity in the CNS. Despite the establishment of extensive expression profiles revealing myeloid cell multiplicity, the local anatomical conditions for the temporal- and spatial-dependent cellular engraftment are poorly understood. Here we highlight recent discoveries of the context-dependent mechanisms of myeloid cell migration and settlement into distinct subtissular structures in the CNS. These insights offer better understanding of the factors needed for compartment-specific myeloid cell recruitment, integration and residence during development and perturbation, which may lead to better treatment of CNS diseases.

    DOI： 10.1038/s41590-022-01415-8

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  • Specification of CNS macrophage subsets occurs postnatally in defined niches Reviewed International coauthorship International journal

    Masuda T, Amann L, Monaco G, Sankowski R, Staszewski O, Krueger M, Del Gaudio F, He L, Paterson N, Nent E, Fernández-Klett F, Yamasaki A, Frosch M, Fliegauf M, Bosch LFP, Ulupinar H, Hagemeyer N, Schreiner D, Dorrier C, Tsuda M, Grothe C, Joutel A, Daneman R, Betsholtz C, Lendahl U, Knobeloch KP, Lämmermann T, Priller J, Kierdorf K, Prinz M

    Nature   604 ( 7907 )   740 - 748   2022.4   （ ISSN:0028-0836 eISSN:1476-4687 ）

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    All tissue-resident macrophages of the central nervous system (CNS)-including parenchymal microglia, as well as CNS-associated macrophages (CAMs1) such as meningeal and perivascular macrophages2-7-are part of the CNS endogenous innate immune system that acts as the first line of defence during infections or trauma2,8-10. It has been suggested that microglia and all subsets of CAMs are derived from prenatal cellular sources in the yolk sac that were defined as early erythromyeloid progenitors11-15. However, the precise ontogenetic relationships, the underlying transcriptional programs and the molecular signals that drive the development of distinct CAM subsets in situ are poorly understood. Here we show, using fate-mapping systems, single-cell profiling and cell-specific mutants, that only meningeal macrophages and microglia share a common prenatal progenitor. By contrast, perivascular macrophages originate from perinatal meningeal macrophages only after birth in an integrin-dependent manner. The establishment of perivascular macrophages critically requires the presence of arterial vascular smooth muscle cells. Together, our data reveal a precisely timed process in distinct anatomical niches for the establishment of macrophage subsets in the CNS.

    DOI： 10.1038/s41586-022-04596-2

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  • A spinal microglia population involved in remitting and relapsing neuropathic pain Reviewed International coauthorship International journal

    Kohno K, Shirasaka R, Yoshihara K, Mikuriya S, Tanaka K, Takanami K, Inoue K, Sakamoto H, Ohkawa Y, Masuda T, Tsuda M

    Science   376 ( 6588 )   86 - 90   2022.4   （ ISSN:0036-8075 eISSN:1095-9203 ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Association for the Advancement of Science ({AAAS})  

    Neuropathic pain is often caused by injury and diseases that affect the somatosensory system. Although pain development has been well studied, pain recovery mechanisms remain largely unknown. Here, we found that CD11c-expressing spinal microglia appear after the development of behavioral pain hypersensitivity following nerve injury. Nerve-injured mice with spinal CD11c+ microglial depletion failed to recover spontaneously from this hypersensitivity. CD11c+ microglia expressed insulin-like growth factor-1 (IGF1), and interference with IGF1 signaling recapitulated the impairment in pain recovery. In pain-recovered mice, the depletion of CD11c+ microglia or the interruption of IGF1 signaling resulted in a relapse in pain hypersensitivity. Our findings reveal a mechanism for the remission and recurrence of neuropathic pain, providing potential targets for therapeutic strategies.

    DOI： 10.1126/science.abf6805

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  • Novel Hexb-based tools for studying microglia in the CNS Reviewed International coauthorship

    Nature Immunology   21 ( 7 )   802 - 815   2020.7

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41590-020-0707-4

  • Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution. Reviewed International coauthorship

    Nature   2019.2

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    Authorship：Lead author   Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41586-019-0924-x

  • Dorsal horn neurons release extracellular ATP in a VNUT-dependent manner that underlies neuropathic pain. Reviewed International coauthorship

    Masuda T, Ozono Y, Mikuriya S, Kohro Y, Tozaki-Saitoh H, Iwatsuki K, Uneyama H, Ichikawa R, Salter MW, Tsuda M, Inoue K

    Nature communications   7   2016.8

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    Authorship：Lead author   Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ncomms12529

  • Transcription factor IRF5 drives P2X4R+-reactive microglia gating neuropathic pain. Reviewed International coauthorship

    Masuda T, Iwamoto S, Yoshinaga R, Tozaki-Saitoh H, Nishiyama A, Mak TW, Tamura T, Tsuda M, Inoue K

    Nature communications   5   2014.5

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    Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ncomms4771

  • Redefining the ontogeny of hyalocytes as yolk sac-derived tissue-resident macrophages of the vitreous body. Reviewed International coauthorship International journal

    Dennis-Dominik Rosmus, Jana Koch, Annika Hausmann, Aude Chiot, Franz Arnhold, Takahiro Masuda, Katrin Kierdorf, Stefanie Marie Hansen, Heidrun Kuhrt, Janine Fröba, Julian Wolf, Stefaniya Boneva, Martin Gericke, Bahareh Ajami, Marco Prinz, Clemens Lange, Peter Wieghofer

    Journal of neuroinflammation   21 ( 1 )   168 - 168   2024.7   （ eISSN:1742-2094 ）

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    BACKGROUND: The eye is a highly specialized sensory organ which encompasses the retina as a part of the central nervous system, but also non-neural compartments such as the transparent vitreous body ensuring stability of the eye globe and a clear optical axis. Hyalocytes are the tissue-resident macrophages of the vitreous body and are considered to play pivotal roles in health and diseases of the vitreoretinal interface, such as proliferative vitreoretinopathy or diabetic retinopathy. However, in contrast to other ocular macrophages, their embryonic origin as well as the extent to which these myeloid cells might be replenished by circulating monocytes remains elusive. RESULTS: In this study, we combine transgenic reporter mice, embryonic and adult fate mapping approaches as well as parabiosis experiments with multicolor immunofluorescence labeling and confocal laser-scanning microscopy to comprehensively characterize the murine hyalocyte population throughout development and in adulthood. We found that murine hyalocytes express numerous well-known myeloid cell markers, but concomitantly display a distinct immunophenotype that sets them apart from retinal microglia. Embryonic pulse labeling revealed a yolk sac-derived origin of murine hyalocytes, whose precursors seed the developing eye prenatally. Finally, postnatal labeling and parabiosis established the longevity of hyalocytes which rely on Colony Stimulating Factor 1 Receptor (CSF1R) signaling for their maintenance, independent of blood-derived monocytes. CONCLUSION: Our study identifies hyalocytes as long-living progeny of the yolk sac hematopoiesis and highlights their role as integral members of the innate immune system of the eye. As a consequence of their longevity, immunosenescence processes may culminate in hyalocyte dysfunction, thereby contributing to the development of vitreoretinal diseases. Therefore, myeloid cell-targeted therapies that convey their effects through the modification of hyalocyte properties may represent an interesting approach to alleviate the burden imposed by diseases of the vitreoretinal interface.

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  • Spatiotemporal dynamics of the CD11c+ microglial population in the mouse brain and spinal cord from developmental to adult stages. Reviewed International journal

    Kohei Nomaki, Risako Fujikawa, Takahiro Masuda, Makoto Tsuda

    Molecular brain   17 ( 1 )   24 - 24   2024.5   （ eISSN:1756-6606 ）

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    CD11c-positive (CD11c+) microglia have attracted considerable attention because of their potential implications in central nervous system (CNS) development, homeostasis, and disease. However, the spatiotemporal dynamics of the proportion of CD11c+ microglia in individual CNS regions are poorly understood. Here, we investigated the proportion of CD11c+ microglia in six CNS regions (forebrain, olfactory bulb, diencephalon/midbrain, cerebellum, pons/medulla, and spinal cord) from the developmental to adult stages by flow cytometry and immunohistochemical analyses using a CD11c reporter transgenic mouse line, Itgax-Venus. We found that the proportion of CD11c+ microglia in total microglia varied between CNS regions during postnatal development. Specifically, the proportion was high in the olfactory bulb and cerebellum at postnatal day P(4) and P7, respectively, and approximately half of the total microglia were CD11c+. The proportion declined sharply in all regions to P14, and the low percentage persisted over P56. In the spinal cord, the proportion of CD11c+ microglia was also high at P4 and declined to P14, but increased again at P21 and thereafter. Interestingly, the distribution pattern of CD11c+ microglia in the spinal cord markedly changed from gray matter at P4 to white matter at P21. Collectively, our findings reveal the differences in the spatiotemporal dynamics of the proportion of CD11c+ microglia among CNS regions from early development to adult stages in normal mice. These findings improve our understanding of the nature of microglial heterogeneity and its dynamics in the CNS.

    DOI： 10.1186/s13041-024-01098-2

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  • Common principles of macrophage biology in blood–tissue barriers Invited Reviewed

    Hiraga S.i., Masuda T.

    Clinical and Experimental Neuroimmunology   2024

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clinical and Experimental Neuroimmunology  

    Blood–tissue barriers play crucial roles in specialized tissues such as the central nervous system (CNS), eye, testis, and placenta. Tissue-resident macrophages in these tissues are indispensable for maintaining tissue homeostasis and responding to pathological conditions. Recent advances in high-throughput and high-dimensional single-cell analysis techniques, coupled with fate-mapping tools, have revealed a remarkable diversity of tissue-resident macrophages at the blood–tissue barrier. However, while comprehensive expression profiling has revealed the heterogeneity of macrophages within individual tissues, the commonalities of macrophages across anatomically similar structures like blood–tissue barriers remain poorly understood. This review focuses on the diversity and functional specialization of macrophages in tissues with blood–tissue barriers, highlighting recent insights into their anatomical distribution, developmental origins, phenotypic characteristics, and roles in maintaining tissue homeostasis. These findings may deepen our understanding of macrophage adaptation mechanisms in tissues with blood–tissue barriers, potentially leading to improved therapies for related disorders. Furthermore, examining the similarities and differences of macrophages across tissues may elucidate the molecular underpinnings of tissue-specific adaptation mechanisms and functional specialization.

    DOI： 10.1111/cen3.12812

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  • Direct neuronal conversion of microglia/macrophages reinstates neurological function after stroke. Reviewed International coauthorship International journal

    Takashi Irie, Taito Matsuda, Yoshinori Hayashi, Kanae Matsuda-Ito, Akihide Kamiya, Takahiro Masuda, Marco Prinz, Noriko Isobe, Jun-Ichi Kira, Kinichi Nakashima

    Proceedings of the National Academy of Sciences of the United States of America   120 ( 42 )   e2307972120   2023.10   （ ISSN:0027-8424 eISSN:1091-6490 ）

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    Although generating new neurons in the ischemic injured brain would be an ideal approach to replenish the lost neurons for repairing the damage, the adult mammalian brain retains only limited neurogenic capability. Here, we show that direct conversion of microglia/macrophages into neurons in the brain has great potential as a therapeutic strategy for ischemic brain injury. After transient middle cerebral artery occlusion in adult mice, microglia/macrophages converge at the lesion core of the striatum, where neuronal loss is prominent. Targeted expression of a neurogenic transcription factor, NeuroD1, in microglia/macrophages in the injured striatum enables their conversion into induced neuronal cells that functionally integrate into the existing neuronal circuits. Furthermore, NeuroD1-mediated induced neuronal cell generation significantly improves neurological function in the mouse stroke model, and ablation of these cells abolishes the gained functional recovery. Our findings thus demonstrate that neuronal conversion contributes directly to functional recovery after stroke.

    DOI： 10.1073/pnas.2307972120

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  • A comparative analysis of microglial inducible Cre lines Reviewed International coauthorship International journal

    Travis E Faust, Philip A Feinberg, Ciara O'Connor, Riki Kawaguchi, Andrew Chan, Hayley Strasburger, Maximilian Frosch, Margaret A Boyle, @Takahiro Masuda, Lukas Amann, Klaus-Peter Knobeloch, Marco Prinz, Anne Schaefer, Dorothy P Schafer

    Cell Reports   42 ( 9 )   113031 - 113031   2023.8   （ ISSN:2211-1247 ）

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    Cre/loxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. Microglial biology has particularly benefited because microglia historically have been difficult to transduce with virus or electroporation methods for gene delivery. Here, we investigate five of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency, cell-type specificity, and spontaneous recombination, depending on the Cre line and inter-loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency, particularly in microglia. There is increasing evidence that microglia are key regulators of neural circuits and major drivers of a broad range of neurological diseases. Reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field and the development of microglia-based therapeutics.

    DOI： 10.1016/j.celrep.2023.113031

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  • Lipid in microglial biology - from material to mediator. Invited Reviewed International journal

    Shota Yamamoto, Takahiro Masuda

    Inflammation and regeneration   43 ( 1 )   38 - 38   2023.7   （ ISSN:1880-9693 eISSN:1880-8190 ）

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    Microglia are resident macrophages in the central nervous system (CNS) that play various roles during brain development and in the pathogenesis of CNS diseases. Recently, reprogramming of cellular energetic metabolism in microglia has drawn attention as a crucial mechanism for diversification of microglial functionality. Lipids are highly diverse materials and crucial components of cell membranes in every cell. Accumulating evidence has shown that lipid and its metabolism are tightly involved in microglial biology. In this review, we summarize the current knowledge about microglial lipid metabolism in health and disease.

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  • Preface Invited

    Masuda Takahiro

    Folia Pharmacologica Japonica   158 ( 4 )   297 - 297   2023.7   （ ISSN:00155691 eISSN:13478397 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：The Japanese Pharmacological Society  

    DOI： 10.1254/fpj.22153

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  • Cellular and molecular heterogeneity of CNS macrophages in health and disease Invited

    Masuda Takahiro

    Folia Pharmacologica Japonica   158 ( 4 )   308 - 311   2023.7   （ ISSN:00155691 eISSN:13478397 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：The Japanese Pharmacological Society  

    <p>The central nervous system (CNS) is a highly complex collection of various cell-types, such as neurons, glial cells, vascular cells, and immune cells, and their complex and dynamic interactions enable to achieve highly sophisticated functions of the CNS. Among such CNS cells are microglia, which are well-known primary CNS macrophages localized in the CNS parenchyma and play a pivotal role in the maintenance of tissue homeostasis. Besides microglia, there are anatomically distinct macrophage populations at the border of the CNS, such as meninge, and perivascular space, called CNS-associated macrophages (CAMs). Recent studies have given novel insights into the nature of CAMs. In this review, I will discuss our current knowledge of the origins, the cellular properties of CNS macrophages.</p>

    DOI： 10.1254/fpj.22152

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  • Microglial diversity in neuropathic pain Invited Reviewed

    Makoto Tsuda, Takahiro Masuda, Keita Kohno

    Trends in Neurosciences   46 ( 7 )   597 - 610   2023.7   （ ISSN:0166-2236 eISSN:1878-108X ）

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    Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

    DOI： 10.1016/j.tins.2023.05.001

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  • Lineage tracing identifies in vitro microglia-to-neuron conversion by NeuroD1 expression. Reviewed International coauthorship International journal

    Takashi Irie, Kanae Matsuda-Ito, Taito Matsuda, Takahiro Masuda, Marco Prinz, Noriko Isobe, Kinichi Nakashima

    Genes to cells : devoted to molecular & cellular mechanisms   28 ( 7 )   526 - 534   2023.7   （ ISSN:1356-9597 eISSN:1365-2443 ）

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    Neuronal regeneration to replenish lost neurons after injury is critical for brain repair. Microglia, brain-resident macrophages that have the propensity to accumulate at the site of injury, can be a potential source for replenishing lost neurons through fate conversion into neurons, induced by forced expression of neuronal lineage-specific transcription factors. However, it has not been strictly demonstrated that microglia, rather than central nervous system-associated macrophages, such as meningeal macrophages, convert into neurons. Here, we show that NeuroD1-transduced microglia can be successfully converted into neurons in vitro using lineage-mapping strategies. We also found that a chemical cocktail treatment further promoted NeuroD1-induced microglia-to-neuron conversion. NeuroD1 with loss-of-function mutation, on the other hand, failed to induce the neuronal conversion. Our results indicate that microglia are indeed reprogrammed into neurons by NeuroD1 with neurogenic transcriptional activity.

    DOI： 10.1111/gtc.13033

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  • Ⅱ. CNS-Associated Macrophages and Immune System in the CNS Invited

    Masuda T.

    Gan to kagaku ryoho. Cancer &amp; chemotherapy   50 ( 6 )   690 - 693   2023.6   （ ISSN:03850684 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Publisher：Gan to kagaku ryoho. Cancer &amp; chemotherapy  

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  • Microglial Cytokines Mediate Plasticity Induced by 10 Hz Repetitive Magnetic Stimulation Reviewed International coauthorship

    Eichler, A; Kleidonas, D; Turi, Z; Fliegauf, M; Kirsch, M; Pfeifer, D; Masuda, T; Prinz, M; Lenz, M; Vlachos, A

    JOURNAL OF NEUROSCIENCE   43 ( 17 )   3042 - 3060   2023.4   （ ISSN:0270-6474 eISSN:1529-2401 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1523/JNEUROSCI.2226-22.2023

    Web of Science

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  • Recent topics regarding macrophage in the central nervous system Invited Reviewed

    Takahiro Masuda

    The Journal of Biochemistry   173 ( 3 )   139 - 143   2023.3   （ ISSN:0021-924X eISSN:1756-2651 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Journal of Biochemistry  

    DOI： 10.1093/jb/mvac093

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  • Lineage tracing identifies in vitro microglia-to-neuron conversion by NeuroD1 expression Reviewed International coauthorship International journal

    #Irie T, @Matsuda-Ito K, @Matsuda T, @Masuda T, @Prinz M, @Isobe N, @Nakashima K.

    Genes to Cells   2023.3

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    Language：Japanese   Publishing type：Research paper (scientific journal)  

  • CD206+ macrophages transventricularly infiltrate the early embryonic cerebral wall to differentiate into microglia. Reviewed International coauthorship International journal

    Yuki Hattori, Daisuke Kato, Futoshi Murayama, Sota Koike, Hisa Asai, Ayato Yamasaki, Yu Naito, Ayano Kawaguchi, Hiroyuki Konishi, Marco Prinz, Takahiro Masuda, Hiroaki Wake, Takaki Miyata

    Cell reports   42 ( 2 )   112092 - 112092   2023.2   （ ISSN:2211-1247 ）

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    The relationships between tissue-resident microglia and early macrophages, especially their lineage segregation outside the yolk sac, have been recently explored, providing a model in which a conversion from macrophages seeds microglia during brain development. However, spatiotemporal evidence to support such microglial seeding in situ and to explain how it occurs has not been obtained. By cell tracking via slice culture, intravital imaging, and Flash tag-mediated or genetic labeling, we find that intraventricular CD206+ macrophages, which are abundantly observed along the inner surface of the mouse cerebral wall, frequently enter the pallium at embryonic day 12. Immunofluorescence of the tracked cells show that postinfiltrative macrophages in the pallium acquire microglial properties while losing the CD206+ macrophage phenotype. We also find that intraventricular macrophages are supplied transepithelially from the roof plate. This study demonstrates that the "roof plate→ventricle→pallium" route is an essential path for microglial colonization into the embryonic mouse brain.

    DOI： 10.1016/j.celrep.2023.112092

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  • A comparative analysis of microglial inducible Cre lines. International coauthorship

    Faust TE, Feinberg PA, O'Connor C, Kawaguchi R, Chan A, Strasburger H, Masuda T, Amann L, Knobeloch KP, Prinz M, Schaefer A, Schafer DP

    bioRxiv : the preprint server for biology   2023.1

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    Language：English  

    DOI： 10.1101/2023.01.09.523268

    PubMed

  • Microglia states and nomenclature: A field at its crossroads Reviewed International coauthorship

    Paolicelli, RC; Sierra, A; Stevens, B; Tremblay, ME; Aguzzi, A; Ajami, B; Amit, I; Audinat, E; Bechmann, I; Bennett, M; Bennett, F; Bessis, A; Biber, K; Bilbo, S; Blurton-Jones, M; Boddeke, E; Brites, D; Brône, B; Brown, GC; Butovsky, O; Carson, MJ; Castellano, B; Colonna, M; Cowley, SA; Cunningham, C; Davalos, D; De Jager, PL; de Strooper, B; Denes, A; Eggen, BJL; Eyo, U; Galea, E; Garel, S; Ginhoux, F; Glass, CK; Gokce, O; Gomez-Nicola, D; González, B; Gordon, S; Graeber, MB; Greenhalgh, AD; Gressens, P; Greter, M; Gutmann, DH; Haass, C; Heneka, MT; Heppner, FL; Hong, S; Hume, DA; Jung, S; Kettenmann, H; Kipnis, J; Koyama, R; Lemke, G; Lynch, M; Majewska, A; Malcangio, M; Malm, T; Mancuso, R; Masuda, T; Matteoli, M; McColl, BW; Miron, VE; Molofsky, AV; Monje, M; Mracsko, E; Nadjar, A; Neher, JJ; Neniskyte, U; Neumann, H; Noda, M; Peng, B; Peri, F; Perry, VH; Popovich, PG; Pridans, C; Priller, J; Prinz, M; Ragozzino, D; Ransohoff, RM; Salter, MW; Schaefer, A; Schafer, DP; Schwartz, M; Simons, M; Smith, CJ; Streit, WJ; Tay, TL; Tsai, LH; Verkhratsky, A; von Bernhardi, R; Wake, H; Wittamer, V; Wolf, SA; Wu, LJ; Wyss-Coray, T

    NEURON   110 ( 21 )   3458 - 3483   2022.11   （ ISSN:0896-6273 eISSN:1097-4199 ）

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.neuron.2022.10.020

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  • Novel insights into the origin and development of CNS macrophage subsets Invited Reviewed International coauthorship

    Takahiro Masuda, Lukas Amann, Marco Prinz

    Clinical and Translational Medicine   12 ( 11 )   e1096   2022.11   （ ISSN:2001-1326 ）

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Clin Transl Med  

    DOI： 10.1002/ctm2.1096

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  • Mapping the origin and fate of myeloid cells in distinct compartments of the eye by single-cell profiling Reviewed International coauthorship International journal

    Wieghofer P, Hagemeyer N, Sankowski R, Schlecht A, Staszewski O, Amann L, Gruber M, Koch J, Hausmann A, Zhang P, Boneva S, Masuda T, Hilgendorf I, Goldmann T, Boettcher C, Priller J, Rossi FMV, Lange C, Prinz M

    EMBO JOURNAL   40 ( 6 )   2021.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.15252/embj.2020105123

  • Diet-dependent regulation of TGFβ impairs reparative innate immune responses after demyelination Reviewed International coauthorship International journal

    Bosch-Queralt M, Cantuti-Castelvetri L, Damkou A, Schifferer M, Schlepckow K, Alexopoulos I, Lütjohann D, Klose C, Vaculčiaková L, Masuda T, Prinz M, Monroe KM, Di Paolo G, Lewcock JW, Haass C, Simons M

    Nature Metabolism   2021.2

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  • Profiling peripheral nerve macrophages reveals two macrophage subsets with distinct localization, transcriptome and response to injury Reviewed International coauthorship International journal

    Elke Ydens, Lukas Amann, Bob Asselbergh, Charlotte L Scott, Liesbet Martens, Dorine Sichien, Omar Mossad, Thomas Blank, Sofie De Prijck, Donovan Low, @Takahiro Masuda, Yvan Saeys, Vincent Timmerman, Ralf Stumm, Florent Ginhoux, Marco Prinz, Sophie Janssens , Martin Guilliams

    Nature Neuroscience   2020.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41593-020-0618-6

  • Comparative analysis of CreER transgenic mice for the study of brain macrophages: A case study Reviewed International journal

    Louise Chappell-Maor, Masha Kolesnikov, Jung-Seok Kim, Anat Shemer, Zhana Haimon, Jonathan Grozovski, Sigalit Boura-Halfon, @Takahiro Masuda, Marco Prinz, Steffen Jung

    European Journal of Immunology   2020.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/eji.201948342

  • Mapping microglia states in the human brain through the integration of high-dimensional techniques Reviewed

    Nature Neuroscience   2019.12

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41593-019-0532-y

  • A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves Reviewed International journal

    Immunity   2019.6

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.immuni.2019.05.009

  • Macrophage centripetal migration drives spontaneous healing process after spinal cord injury Reviewed International journal

    @Kazu Kobayakawa, @Yasuyuki Ohkawa, @Shingo Yoshizaki, @Tetsuya Tamaru, @Takeyuki Saito, @Ken Kijima, @Kazuya Yokota, @Masamitsu Hara, @Kensuke Kubota, @Yoshihiro Matsumoto, @Katsumi Harimaya, Keiko Ozato, @Takahiro Masuda, @Makoto Tsuda, Tomohiko Tamura, @Kazuhide Inoue, V Reggie Edgerton, Yukihide Iwamoto, @Yasuharu Nakashima, @Seiji Okada

    Science Advances   2019.5

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    DOI： 10.1126/sciadv.aav5086

  • Transcription factor MafB contributes to the activation of spinal microglia underlying neuropathic pain development. Reviewed

    Tozaki-Saitoh H, Masuda J, Kawada R, Kojima C, Yoneda S, Masuda T, Inoue K, Tsuda M

    Glia   67 ( 4 )   729 - 740   2018.11

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/glia.23570

  • Silencing of TGFβ signalling in microglia results in impaired homeostasis. Reviewed

    Zöller T, Schneider A, Kleimeyer C, Masuda T, Potru PS, Pfeifer D, Blank T, Prinz M, Spittau B

    2018.10

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/s41467-018-06224-y

  • Glucocorticoid regulation of ATP release from spinal astrocytes underlies diurnal exacerbation of neuropathic mechanical allodynia Reviewed

    Takahiro Masuda

    Nature Communications   7   2016.12

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/ncomms13102

  • A novel P2X4 receptor-selective antagonist produces anti-allodynic effect in a mouse model of herpetic pain. Reviewed

    Matsumura Y, Yamashita T, Sasaki A, Nakata E, Kohno K, Masuda T, Tozaki-Saitoh H, Imai T, Kuraishi Y, Tsuda M, Inoue K

    Scientific reports   6   2016.8

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/srep32461

  • Transcription factor IRF1 is responsible for IRF8-mediated IL-1β expression in reactive microglia. Reviewed

    128 ( 4 )   216 - 220   2015.8

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    DOI： 10.1016/j.jphs.2015.08.002

  • Chemokine (C-C motif) receptor 5 is an important pathological regulator in the development and maintenance of neuropathic pain. Reviewed

    Matsushita K, Tozaki-Saitoh H, Kojima C, Masuda T, Tsuda M, Inoue K, Hoka S

    Anesthesiology   120 ( 6 )   1491 - 1503   2014.6

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    Language：Others   Publishing type：Research paper (scientific journal)  

    DOI： 10.1097/aln.0000000000000190

  • IRF8 is a transcriptional determinant for microglial motility. Reviewed

    Masuda T, Nishimoto N, Tomiyama D, Matsuda T, Tozaki-Saitoh H, Tamura T, Kohsaka S, Tsuda M, Inoue K

    Purinergic signalling   10 ( 3 )   515 - 521   2014.5

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1007/s11302-014-9413-8

  • IRF8 is a critical transcription factor for transforming microglia into a reactive phenotype. Reviewed

    Masuda T, Tsuda M, Yoshinaga R, Tozaki-Saitoh H, Ozato K, Tamura T, Inoue K

    Cell reports   1 ( 4 )   334 - 340   2012.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1016/j.celrep.2012.02.014

  • Neuronal CCL21 up-regulates microglia P2X4 expression and initiates neuropathic pain development. Reviewed

    Biber K, Tsuda M, Tozaki-Saitoh H, Tsukamoto K, Toyomitsu E, Masuda T, Boddeke H, Inoue K

    The EMBO journal   30 ( 9 )   1864 - 1873   2011.3

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1038/emboj.2011.89

  • IFN-γ receptor signaling mediates spinal microglia activation driving neuropathic pain. Reviewed

    106 ( 19 )   8032 - 8037   2009.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1073/pnas.0810420106

  • Fibronectin/integrin system is involved in P2X(4) receptor upregulation in the spinal cord and neuropathic pain after nerve injury. Reviewed

    Tsuda M, Toyomitsu E, Komatsu T, Masuda T, Kunifusa E, Nasu-Tada K, Koizumi S, Yamamoto K, Ando J, Inoue K

    Glia   56 ( 5 )   579 - 585   2008.4

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/glia.20641

  • Lyn tyrosine kinase is required for P2X(4) receptor upregulation and neuropathic pain after peripheral nerve injury. Reviewed

    Tsuda M, Tozaki-Saitoh H, Masuda T, Toyomitsu E, Tezuka T, Yamamoto T, Inoue K

    Glia   56 ( 1 )   50 - 58   2008.1

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1002/glia.20591

  • Reduced pain behaviors and extracellular signal-related protein kinase activation in primary sensory neurons by peripheral tissue injury in mice lacking platelet-activating factor receptor Reviewed

    Makoto Tsuda, Satoshi Ishii, Takahiro Masuda, Shigeo Hasegawa, Koji Nakamura, Kenichiro Nagata, Tomohiro Yamashita, Hidemasa Furue, Hidetoshi Tozaki-Saitoh, Megumu Yoshimura, Schuichi Koizumi, Takao Shimizu, Kazuhide Inoue

    JOURNAL OF NEUROCHEMISTRY   102 ( 5 )   1658 - 1668   2007.9

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    Language：English   Publishing type：Research paper (scientific journal)  

    DOI： 10.1111/j.1471-4159.2007.04796.x

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Books

  • 実験医学「脳をしなやかに制御するミクログリアと脳内免疫系」　脳実質ミクログリアと脳境界マクロファージ

    @増田隆博（ Role： Joint author）

    羊土社  2022.11 

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    Language：Japanese   Book type：Scholarly book

  • 実験医学「脳をしなやかに制御するミクログリアと脳内免疫系」　概論：多様なミクログリアの機能と細胞特性

    @増田隆博（ Role： Joint author）

    羊土社  2022.11 

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    Language：Japanese   Book type：Scholarly book

  • 「特集」ミクログリアと脳内免疫系/ファージ療法

    増田, 隆博

    羊土社  2022.11    （ ISBN:9784758125611 ）

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    Total pages：p2926-3046   Language：Japanese  

    CiNii Books

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  • 臨床免疫・アレルギー科　特集Ⅱマクロファージの多様性「多様な脳内マクロファージからみる正常脳と中枢神経系疾患」

    @増田隆博（ Role： Joint author）

    科学評論社  2022.8 

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    Responsible for pages：第７８巻　第２号   Language：Japanese   Book type：Scholarly book

  • 実験医学「神経免疫　メカニズムと疾患　神経系と免疫系を結ぶ分子機構の解明からバイオマーカー・治療標的の探索まで」

    @増田隆博（ Role： Joint author）

    羊土社  2021.9 

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    Responsible for pages：Vol.39 No.15, 総論　脳内マクロファージの新時代―多様性が映す中枢性疾患と神経免疫   Language：Japanese   Book type：Scholarly book

  • 実験医学「脳の半分を占める　グリア細胞 脳と心と体をつなぐ“膠」

    @増田隆博（ Role： Joint author）

    羊土社  2019.10 

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    Responsible for pages：Vol.37 No.17, 単一細胞解析により明らかになったミクログリアの時空間的多様性   Language：Japanese   Book type：Scholarly book

  • 癌と化学療法　Central Nervous System Tumor 脳腫瘍　脳腫瘍と免疫システムUpdate　ⅱ脳境界マクロファージと脳免疫システム

    @増田隆博（ Role： Joint author）

    癌と化学療法社  2023.6 

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    Language：Japanese   Book type：Scholarly book

  • 炎症と免疫　特集〈Basic Science〉間質リテラシーと疾患：中枢神経系の間質に常在する脳内マクロファージと疾患

    増田隆博（ Role： Joint author）

    先端医学社  2023.1 

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    Language：Japanese   Book type：Scholarly book

  • 「特集」ミクログリアと脳内免疫系/ファージ療法

    増田 隆博

    羊土社  2022    （ ISBN:9784758125611 ）

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    Language：Japanese  

    CiNii Books

  • Peripheral Nerve Injury: a Mouse Model of Neuropathic Pain

    @Takahiro Masuda, @Yuta Kohro, @Kazuhide Inoue, @Makoto Tsuda（ Role： Joint author）

    Bio-protocol  2017.5 

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    Responsible for pages：Vol 7, Issue 9   Language：English   Book type：Scholarly book

    DOI： https://doi.org/10.21769/BioProtoc.2252

    Other Link： https://bio-protocol.org/e2252

  • 月刊「細胞」　特集「ミクログリアと疼痛」　ミクログリアと神経障害性疼痛

    @増田隆博、@津田誠、@齋藤秀俊、@山下智大、@高露雄太、@井上和秀（ Role： Joint author）

    月刊「細胞」  2016.8 

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    Language：Japanese   Book type：Scholarly book

  • Microglia: Lentiviral transduction of cultured microglia

    @Takahiro Masuda, @Makoto Tsuda, @Hidetoshi Tozaki-Saitoh, @Kazuhide Inoue（ Role： Joint author）

    2013.8 

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    Language：English   Book type：Scholarly book

  • Microglia: Intrathecal infusion of microglia cells

    @Takahiro Masuda, @Makoto Tsuda, @Hidetoshi Tozaki-Saitoh, @Kazuhide Inoue（ Role： Joint author）

    2013.8 

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    Language：English   Book type：Scholarly book

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Presentations

  • 脳内マクロファージの多様性と中枢神経系疾患

    @増田隆博

    第44回日本炎症・再生医学会  2023.7 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：大阪   Country：Japan  

  • 脳内マクロファージの分化や機能制御

    @増田隆博

    第35回日本神経免疫学会学術集会  2023.9 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：東京   Country：Japan  

  • 多様な脳内マクロファージの発生と機能

    @増田隆博

    第96回日本生化学会大会  2023.10 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Microglia and CNS border-associated macrophages-similar but different-

    2023.12 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Understanding diverse macrophages in the central nervous system

    2023.12 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Unraveling the characteristics of macrophages by single-cell analysis

    2023.12 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

    Repository Public URL： https://hdl.handle.net/2324/7174513

  • Novel insights into the ontogeny and diversity of CNS macrophages Invited International conference

    @Takahiro Masuda

    The 9th Japan-China Joint Meeting of Basic and Clinical Pharmacology  2023.7 

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    Event date： 2024.4

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：China  

  • Diverse macrophages sense and govern brain environment Invited International conference

    @Takahiro Masuda

    16th International Society of Neuroimmunology (ISNI)  2023.8 

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    Event date： 2024.4

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Canada  

  • 脳内免疫系による健やかな脳の形成・維持と破綻 Invited

    @増田隆博

    国立大学附置研究所・センター会議特別シンポジウム  2023.12 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：東京   Country：Japan  

  • 脳実質と末梢循環系を繋ぐ脳境界領域の形成維持と免疫細胞の特性 Invited

    @増田隆博

    第12回AAA研究会  2024.1 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：東京   Country：Japan  

  • Diverse macrophages in the central nervous system Invited

    @Takahiro Masuda

    2024.1 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • シングルセル解析によって明らかになった脳内マクロファージの多様性と細胞特性 Invited

    @増田隆博

    文部科学省認定　共同利用・共同研究拠点　横浜市立大学先端医科学研究センター「マルチオミックスによる遺伝子発現制御の先端的医学共同研究拠点」  2024.2 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：横浜   Country：Japan  

  • 脳境界マクロファージの発生と維持メカニズム

    @増田隆博

    第129回日本解剖学会総会・全国学術集会  2024.3 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：沖縄   Country：Japan  

  • Macrophages in the central nervous system: ontogeny and function in health and disease Invited International conference

    2023.2 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 脳内マクロファージと脳の発達

    ＠増田隆博

    第76回日本薬理学会年会  2022.12 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：横浜   Country：Japan  

  • Diversity of brain macrophages in health and disease Invited International conference

    @Takahiro Masuda

    5th Japan-UK Neuroscience Symposium  2022.9 

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    Event date： 2022.9

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 多様な脳内マクロファージから紐解く中枢神経系疾患

    @増田隆博

    第43回日本炎症・再生医学会  2022.7 

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    Event date： 2022.7

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：淡路島   Country：Japan  

  • Diverse macrophages govern brain environment

    @Takahiro Masuda

    Neuro2022  2022.8 

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    Event date： 2022.6 - 2022.7

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Decoding brain environment through single-cell analysis of microglia

    @Takahiro Masuda

    2022.3 

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    Event date： 2022.3

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 正常時および病態時における中枢神経系マクロファージの多様性

    @増田隆博

    第95回日本薬理学会年会  2022.3 

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    Event date： 2022.3

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：福岡国際会議場   Country：Japan  

  • 脳実質ミクログリアと脳境界マクロファージ Invited

    ＠増田隆博

    第43回日本疼痛学会  2021.12 

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    Event date： 2022.1

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：オンライン   Country：Japan  

  • マウスおよびヒト脳内におけるミクログリアの多様性および可塑性 Invited

    @増田隆博

    第94回日本生化学会大会  2021.11 

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    Event date： 2022.1

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：オンライン   Country：Japan  

  • Diversity and plasticity of microglia in mice and human Invited

    @Takahiro Masuda

    2021.12 

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    Event date： 2022.1

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Single-cell analysis reveals spatial and temporal heterogeneity of microglia in human and mice Invited International conference

    @Takahiro Masuda

    2020.9 

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    Event date： 2020.9

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Microglia heterogeneity and plasticity revealed by single cell analysis Invited

    2019.12 

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    Event date： 2019.12

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 脳境界免疫細胞を標的とした疾患研究の可能性 Invited

    @増田隆博

    AMED精神・神経疾患領域/早期ライフ連携推進ワークショップ  2023.8 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 脳内マクロファージの多様性と機能 Invited

    @増田隆博

    次世代薬理学セミナー2023(日本薬理学会西南部会)  2023.10 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：オンライン   Country：Japan  

  • Diverse macrophages and brain development Invited International conference

    @Takahiro Masuda

    Young Glia  2023.10 

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    Event date： 2024.4

    Language：English   Presentation type：Oral presentation (general)  

    Country：Japan  

  • Genetic tools for studying diverse macrophages in the CNS International conference

    @Takahiro Masuda

    The 50th Naito Conference  2023.10 

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    Event date： 2024.4

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Similar but different: Diverse macrophages in the central nervous system Invited International conference

    @Takahiro Masuda

    The 32th Hot Spring Harbor International Symposium  2023.9 

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    Event date： 2024.4

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • 脳内マクロファージの細胞特性や機能を解く Invited

    @増田隆博

    第8回日本骨免疫学会ウィンタースクール  2024.1 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：長野   Country：Japan  

  • 多様な脳内マクロファージの細胞特性を理解する

    @増田隆博

    第13回日本マーモセット研究会大会  2024.2 

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    Event date： 2024.4

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：東京   Country：Japan  

  • Ontogeny and function of diverse brain macrophages Invited

    @Takahiro Masuda

    International Biomedical Research Seminars  2023.5 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Country：Japan  

  • 多様なマクロファージから脳を知り、制御する Invited

    @増田隆博

    2022.10 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：オンライン   Country：Japan  

  • 多様な脳内マクロファージから脳の形成と異常を理解する Invited

    ＠増田隆博

    第16大阪大学ニコンイメージングセンター　シリーズセミナー  2023.2 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (invited, special)  

    Venue：大阪   Country：Japan  

  • 多様な脳内マクロファージから見る脳の形成と機能 Invited

    ＠増田隆博

    第15回　CBIR/ONSA/大学院セミナー共催 若手インスパイアシンポジウム  2023.2 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：オンライン   Country：Japan  

  • 多様な脳内マクロファージの成り立ちとその後の変化 Invited

    ＠増田隆博

    令和4年度「感染・免疫・がん・炎症」全国共同研究拠点シンポジウム  2023.3 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Symposium, workshop panel (public)  

    Venue：北海道   Country：Japan  

  • 脳内マクロファージの多様性と中枢神経系疾患

    ＠増田隆博

    合田パネル第3回創発の場  2023.3 

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    Event date： 2023.5

    Language：Japanese   Presentation type：Oral presentation (general)  

    Country：Japan  

  • 多様な脳内マクロファージから見る脳形成と中枢神経系疾患 Invited

    @増田隆博

    第10回神経と免疫を語る会  2022.7 

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    Event date： 2022.7

    Language：Japanese   Presentation type：Oral presentation (general)  

    Country：Japan  

  • 脳の中に存在する多様なマクロファージを知る Invited

    増田隆博

    第２２回NCU Life Science Seminar  2022.8 

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    Event date： 2022.6

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：名古屋市立大学   Country：Japan  

  • 多様な脳内マクロファージと治療標的としての可能性 Invited

    @増田隆博

    第2回SAMURAI研究会  2022.2 

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    Event date： 2022.2

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：オンライン   Country：Japan  

  • IRF family transcription factor axis regulates gene expression program in microglia that gates neuropathic pain

    2012.7 

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    Event date： 2012.7

    Language：Japanese  

    Country：Japan  

  • IRF Family Transcription Factor Axis Governs Gene Expression Program in Microglia Gating Neuropathic Pain International conference

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Nao Nishimoto, Shosuke Iwamoto, Hidetoshi Tozaki-Saitoh, Tomohiko Tamura, Kazuhide Inoue

    Purine2012  2012.6 

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    Event date： 2012.5 - 2012.6

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • IRF family transcription factor axis governs gene expression program in microglia that drives neuropathic pain.

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Nao Nishimoto, Shosuke Iwamoto, Tomohiko Tamura, Kazuhide Inoue

    2012.3 

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    Event date： 2012.3

    Language：English   Presentation type：Oral presentation (general)  

    Country：Japan  

  • 転写因子IRF8を介したミクログリアATP受容体発現制御および神経障害性疼痛における役割

    増田隆博、津田誠、吉永遼平、齊藤秀俊、田村智彦、井上和秀

    プリン研究会  2011.10 

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    Event date： 2011.10

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：岡崎   Country：Japan  

    神経障害などに伴った中枢性疾患発症時、ミクログリアはATP受容体や細胞内シグナル分子を過剰発現させ、炎症性サイトカインなどの生理活性液性因子を過剰産生・放出するなど、劇的にfunctional phenotype shiftを遂げ、「過活動」状態へと移行する。こうした過活動ミクログリアは、神経障害性疼痛発症においても重要な役割を果たしていることは明らかになっているが、ミクログリアの過活動状態への移行を司る遺伝子発現メカニズムは未だ明らかになっていない。本研究で、我々はInterferon regulatory factor-8(IRF8)がミクログリアの過活動状態への移行に重要な役割を果たしていることを見出した。
    末梢神経損傷後、脊髄内でミクログリア特異的にIRF8の顕著な発現増加が観察された。一方、培養ミクログリア細胞にIRF8を強制発現させたところ、P2X4受容体やP2Y12受容体の顕著な発現増加が観察されるなど、過活動状態ミクログリアに見られる特徴的変化を示した。しかし、DNA結合能力の消失した変異型IRF8を遺伝子導入した際には、こうした変化は見られなかった。また、IRF8欠損マウスにおいては、野生型マウスと比較して、末梢神経損傷後に観察されるミクログリア関連分子(P2X4受容体やP2Y12受容体など)の発現増加および疼痛症状が有意に抑制された。以上の結果から、末梢神経損傷後に脊髄ミクログリアで発現増加したIRF8は、ミクログリアの過活動状態への移行に関与し、神経障害性疼痛発症に重要な役割を果たしていると考えられる。

  • Interferon regulatory factor-8 in spinal microglia is a transcription factor crucial for switching to a reactive phenotype after nerve injury

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Hidetoshi Tozaki-Saitoh, Tomohiko Tamura, Kazuhide Inoue

    2011.9 

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    Event date： 2011.9

    Language：English   Presentation type：Oral presentation (general)  

    Country：Japan  

  • IRF8 transcription factor directs microglia to be a hyperactive phenotype driving neuropathic pain International conference

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Hidetoshi Tozaki-Saitoh, Tomohiko Tamura, Kazuhide Inoue

    EuroGlia 2011  2011.9 

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    Event date： 2011.9

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Czech Republic  

  • 転写因子IRF8によるミクログリアの活動性制御および神経障害性疼痛における役割 Invited

    増田隆博、津田誠、吉永遼平、齊藤秀俊、田村智彦、井上和秀

    生理研研究会・グリア細胞機能から迫る脳機能解明  2011.6 

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    Event date： 2011.6

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：岡崎   Country：Japan  

    神経損傷などに伴う中枢性疾患発症時、ミクログリアは細胞機能を司る受容体や細胞内シグナル分子を過剰発現させ、炎症性サイトカインなどの生理活性液性因子を過剰産生・放出するなど、劇的にfunctional phenotype shiftを遂げ、「過活動」状態になる。こうしたミクログリアは、神経障害性疼痛発症においても重要な役割を果たしていることは明らかになっているが、ミクログリアを過活動状態へと移行させる遺伝子発現メカニズムは未だ明らかになっていない。今回、我々はInterferon regulatory factor-8(IRF8)がミクログリアの過活動状態への移行に重要な役割を果たしていることを見出した。
    末梢神経損傷後、脊髄内でミクログリア特異的にIRF8の発現増加が観察された。一方、レンチウィルスベクターを用いて培養ミクログリア細胞にIRF8を強制発現させたところ、機能分子の発現増加など、過活動状態ミクログリアに見られる特徴的変化を示した。しかし、DNA結合能力の消失した変異体IRF8を遺伝子導入した際には、こうした変化は見られなかった。また、IRF8欠損マウスにおいては、野生型マウスと比較して、神経損傷後のミクログリア関連分子の発現増加および疼痛症状が有意に抑制された。以上の結果から、末梢神経損傷後に脊髄ミクログリアで発現増加したIRF8は、ミクログリアの過活動状態への移行に関与し、神経障害性疼痛発症に重要な役割を果たしていると考えられる。

  • IRF8 transcription factor governs gene expression program in microglia that drives neuropathic pain after peripheral nerve injury

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Tomohiko Tamura, Kazuhide Inoue

    2011.3 

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    Event date： 2011.3

    Language：English  

    Country：Japan  

  • 転写因子interferon regulatory factor-8 (IRF8) の神経障害性疼痛における役割

    増田隆博

    第６回九大痛みの研究会  2011.2 

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    Event date： 2011.2

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：福岡   Country：Japan  

  • Interferon regulatory factor-8 in spinal microglia is a transcription factor crucial for the development of neuropathic pain International conference

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Tomohiko Tamura*, Kazuhide Inoue

    GLIA WORLD  2010.10 

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    Event date： 2010.10

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Interferon regulatory factor-8はミクログリア由来疼痛関連分子の発現を誘導する転写因子である

    2010.9 

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    Event date： 2010.9

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：神戸   Country：Japan  

    Neuropathic pain occurs after several diseases accompanied by nerve damage, which is characterized by abnormal sensory perception such as tactile allodynia (hypersensitivity to innocuous mechanical stimuli). This debilitating pain condition arises as a consequence of excessive excitability of neurons in spinal dorsal horn, and the neuronal hyperexcitability involves signaling from activated spinal microglia that induce or enhance expression of various genes including proinflammatory cytokines. However, a key transcription factor regulating gene expression and neuropathic pain states is not identified. In the present study, we examined the role of interferon regulatory factor-8 (IRF-8), a member of IRF family transcription factor, in regulating tactile allodynia. We found that peripheral nerve injury (PNI) increased the expression of IRF-8 in spinal microglia in a cell type-specific manner. Furthermore, mice lacking IRF-8 (irf8-/-) exhibited a marked reduction in allodynia after PNI compared with wild-type mice without affecting normal pain sensitivity or responses to cold stimuli. In contrast, these mice showed a similar pain behavior in an inflammatory chronic pain model. Interestingly, irf8-/- mice failed to increase the expression of genes crucial for producing pain hypersensitivity in the spinal cord following PNI. Together, our present findings suggest that IRF-8 critically contributes to the pathogenesis of neuropathic pain but not of inflammatory pain.

  • Role of interferon regulatory factor-8 in the pathogenesis of neuropathic pain International conference

    Takahiro Masuda, Makoto Tsuda, Ryohei Yoshinaga, Tomohiko Tamura, Kazuhide Inoue

    Purine 2010  2010.6 

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    Event date： 2010.5 - 2010.6

    Language：English   Presentation type：Oral presentation (general)  

    Country：Spain  

  • 神経障害性疼痛におけるinterferon regulatory factor-8の役割

    第８３回日本薬理学会年会  2010.3 

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    Event date： 2010.3

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：大阪   Country：Japan  

    Following peripheral nerve injury (PNI), spinal microglia become activated and are implicated in producing neuropathic pain. Activated microglia induce or enhance expression of various genes (such as proinflammatory cytokines), but a key transcriptional factor in spinal microglia that drives neuropathic pain is not identified. In the present study, we found that PNI increased the expression of interferon regulatory factor-8 (IRF-8), a transcription factor, in the spinal cord microglia. Furthermore, mice lacking IRF-8 exhibited a marked reduction in tactile allodynia (hypersensitivity to innocuous mechanical stimuli) after PNI compared to wild-type littermates without affecting basal pain sensitivity. Interestingly, these mice also failed to increase the expression of crucial factors for producing pain hypersensitivity in the spinal cord. Together, our present findings suggest that IRF-8 critically contributes to the pathogenesis of neuropathic pain after PNI.

  • Interferon-gamma receptor signals are required for spinal microglia activation and neuropathic pain after peripheral nerve injury International conference

    Takahiro Masuda, Makoto Tsuda, Kazuhide Inoue

    Fukuoka Purine 2009  2009.7 

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    Event date： 2009.7

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Country：Japan  

  • Lyn tyrosine kinase is essential for interferon-γ-dependent spinal microglia activation driving neuropathic pain

    第８２回日本薬理学会年会  2009.3 

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    Event date： 2009.3

    Language：English   Presentation type：Oral presentation (general)  

    Venue：横浜   Country：Japan  

    After peripheral nerve injury, spinal microglia become activated form, which are critical for producing abnormal pain hypersensitivity, namely allodynia - a hallmark symptom of neuropathic pain. We have previously shown that in normal animals spinal microglia express interferon-γ (IFN-γ) receptors and that stimulating these receptors drive microglia to transform into activated ones and that mice lacking IFN-γ receptor exhibit impaired nerve injury-induced microglia activation and allodynia. However, the detailed mechanisms of IFN-γ-induced microglia activation remain unknown. In this study, we investigated the role of Lyn tyrosine kinase that is implicated in neuropathic pain. We found that intrathecal administration of IFN-γ upregulated the expression of Lyn in spinal microglia. In Lyn-deficient mice (lyn-/-), IFN-γ failed to activate microglia and to generate allodynic behavior. Furthermore, nerve injury-induced activation of microglia in the spinal dorsal horn was markedly suppressed in lyn-/- mice compared to wild-type mice. Together, our findings suggest that IFN-γ produces activation of microglia via Lyn kinase signaling, which in turn leads to allodynia after nerve injury.

  • Interferon-γ and Lyn tyrosine kinase are required for spinal microglia activation and neuropathic pain after peripheral nerve injury International conference

    2008.11 

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    Event date： 2008.11

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：ワシントン   Country：United States  

    Neuropathic pain is a result of peripheral nerve injury in diabetes or cancer. A hallmark of this pain is abnormal sensory perception of pain such as allodynia (hypersensitivity to light stimuli). Spinal microglia exhibiting activated form (proliferation, hypertrophy of their cell bodies) have a crucial role in producing allodynia after nerve injury. We have previously shown that a single intrathecal administration of interferon-γ (IFN-γ) to normal animals produces progressive allodynia and spinal microglia activation and that mice lacking IFN-γ receptor display impaired nerve injury-induced microglia activation and allodynia. However, the detailed mechanisms of IFN-γ-dependent microglia activation remain unknown. In the present study, we examined the role of Lyn tyrosine kinase, upregulated in the spinal cord and involved in generating neuropathic allodynia after nerve injury. We found that intrathecal administration of IFN-γ upregulated the expression of Lyn in spinal microglia. In wild-type (WT) mice, intrathecal IFN-γ injection produced an increase in the number of microglia in the dorsal horn and allodynic behavior. In contrast, these changes were markedly suppressed in Lyn-deficient mice (lyn-/-). Furthermore, nerve injury-induced proliferation of microglia in the ipsilateral dorsal horn in WT mice was also attenuated in lyn-/- mice. Together, our findings suggest that IFN-γ produces the activation of microglia via Lyn kinase signaling, which in turn leads to allodynia after peripheral nerve injury.

  • 末梢神経損傷によるミクログリアの活性化と神経因性疼痛発症におけるIFN-γの役割

    福岡ペイン２００８  2008.7 

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    Event date： 2008.7

    Language：Japanese   Presentation type：Oral presentation (general)  

    Venue：Fukuoka   Country：Japan  

    癌や糖尿病などにより神経が損傷を受けることで、神経因性疼痛が発症する。この疼痛は、非侵害性刺激によって激烈な痛みを感じてしまうアロディニアが特徴的である。近年、我々は神経損傷後に脊髄内で活性化したミクログリアが神経因性疼痛発症に重要な役割を持つことを明らかにしてきた。しかし、これまでにミクログリア活性化の詳細なメカニズムは明らかになっていない。そこで本研究では、神経損傷後に脊髄内で発現増加することが報告されているインターフェロンγ（IFN-γ）に着目し、神経因性疼痛発症およびミクログリア活性化への関与について検討した。
    IFN-γリコンビナントタンパク質を脊髄腔内投与することにより、強力かつ持続的なアロディニア症状を呈した。また、脊髄内でのIFN-γ受容体mRNA発現細胞はミクログリアのみであったことから、IFN-γ処置動物の脊髄におけるミクログリアを免疫染色法で観察した。その結果、ミクログリアは異常な活性化（増殖・細胞体の肥大化）を起こしていることが明らかになった。
    続いて、IFN-γ受容体欠損マウスと用いて検討を行ったところ、野生型マウスに比べ、神経損傷後のアロディニア症状および損傷側脊髄後角でのミクログリア活性化に劇的な改善が観察された。
    以上のことより、末梢神経損傷により脊髄内で発現増加するIFN-γは直接ミクログリアに作用し、その活性化を介して神経因性疼痛発症に重要な役割を持つことが明らかになった。

  • Role of interferon-γ in spinal microglia activation and neuropathic pain after peripheral nerve injury International conference

    2008.7 

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    Event date： 2008.7

    Language：English  

    Venue：Fukuoka   Country：Japan  

    Neuropathic pain is a result of peripheral nerve injury in diabetes or cancer. A hallmark of this pain is abnormal sensory perception of pain such as allodynia (hypersensitivity to light stimuli). We have previously shown that spinal microglia exhibiting activated form have a crucial role in producing allodynia after nerve injury. However, the mechanisms of microglia activation remain unknown. In the present study, we examined the role of interferon-γ (IFN-γ), reported to be upregulated in the spinal cord of animal models of neuropathic pain, in microglial activation and neuropathic allodynia. We found that intrathecal administration of IFN-γ produced long-lasting allodynia. The expression of IFN-γ receptor mRNA in the spinal cord of naïve rats was present only in microglia. In the dorsal horn of IFN-γ-treated rats, microglia dramatically changed their morphology into hypertrophy and also proliferated, both of which are prominent features of activated microglia. We next examined the role of IFN-γ in tactile allodynia and microglia activation after peripheral nerve injury using mice lacking IFN-γ receptor (ifngr-/-). We found that ifngr-/- mice exhibited a marked reduction in tactile allodynia after nerve injury compared with wild-type (WT) mice. Furthermore, in WT mice, nerve injury increased the number of microglial cells with hypertrophic morphology in the ipsilateral dorsal horn. In contrast, these changes were markedly suppressed in ifngr-/- mice. Together, our present findings suggest that the IFN-γ/IFN-γ receptor system has crucial roles in activating microglia and producing tactile allodynia after nerve injury.

  • Interferon-γ signals were required in spinal microglia activation and neuropathic pain after peripheral nerve injury International conference

    2008.7 

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    Event date： 2008.6 - 2008.7

    Language：English   Presentation type：Symposium, workshop panel (public)  

    Venue：コペンハーゲン   Country：Denmark  

    Neuropathic pain is a result of peripheral nerve injury in diabetes or cancer. A hallmark of this pain is abnormal sensory perception of pain such as allodynia (hypersensitivity to light stimuli). We have previously shown that spinal microglia exhibiting activated form have a crucial role in producing allodynia after nerve injury. However, the mechanisms of microglia activation remain unknown. In the present study, we examined the role of interferon-γ (IFN-γ), reported to be upregulated in the spinal cord of animal models of neuropathic pain, in microglial activation and neuropathic allodynia. We found that intrathecal administration of IFN-γ produced long-lasting allodynia. The expression of IFN-γ receptor mRNA in the spinal cord of naïve rats was present only in microglia. In the dorsal horn of IFN-γ-treated rats, microglia dramatically changed their morphology into hypertrophy and also proliferated, both of which are prominent features of activated microglia. We next examined the role of IFN-γ in tactile allodynia and microglia activation after peripheral nerve injury using mice lacking IFN-γ receptor (ifngr-/-). We found that a strong allodynia and microglia activation in spinal dorsal horn were markedly attenuated in ifngr-/- mice compared with wild-type (WT) mice. We also found that P2X4 receptor deficient mice failed to exhibit allodynic behavior as observed in WT mice after intrathecal IFN-γ administration. Together, our present findings suggest that the IFN-γ/IFN-γ receptor system has crucial roles in activating microglia, and producing tactile allodynia presumably via P2X4 receptor after nerve injury.

  • 脳内炎症制御の分子基盤　脳内マクロファージの分化や機能制御

    増田 隆博

    神経免疫学  2023.9  (一社)日本神経免疫学会

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    Language：Japanese  

  • 神経-免疫および炎症性相互作用　CNSマクロファージのサブセットの特定は出生後に境界明瞭なニッチにおいて生じる(Neuro-immune and inflammatory interaction　Specification of CNS macrophage subsets occurs postnatally in defined niches)

    Masuda Takahiro, Prinz Marco

    日本免疫学会総会・学術集会記録  2022.11  (NPO)日本免疫学会

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    Language：English  

  • 炎症が引き起こす線維化と組織修復　KAI-JSI Joint Session　中枢神経系における多様なマクロファージ(Inflammation driven fibrosis and tissue repair: KAI-JSI Joint Session　Diverse macrophages in the central nervous system)

    Masuda Takahiro

    日本免疫学会総会・学術集会記録  2023.12  (NPO)日本免疫学会

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    Language：English  

  • ミクログリアによる脳情報デコード　ミクログリアのシングルセル解析による脳環境デコーディング(Microglial decoding of brain information　Decoding brain environment through single-cell analysis of microglia)

    Masuda Takahiro

    The Journal of Physiological Sciences  2022.12  (一社)日本生理学会

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  • グリア多様性の理解に基づく精神・神経変性疾患の機序解明と治療法開発　多様な脳内マクロファージの発生と機能

    増田 隆博

    日本生化学会大会プログラム・講演要旨集  2023.10  (公社)日本生化学会

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    Language：Japanese  

  • グリア多様性の理解に基づく精神・神経変性疾患の機序解明と治療法開発　多様な脳内マクロファージの発生と機能

    増田 隆博

    日本生化学会大会プログラム・講演要旨集  2023.10  (公社)日本生化学会

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    Language：Japanese  

  • 脳内炎症制御の分子基盤　脳内マクロファージの分化や機能制御

    増田 隆博

    神経免疫学  2023.9  (一社)日本神経免疫学会

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    Language：Japanese  

  • 神経-免疫および炎症性相互作用　CNSマクロファージのサブセットの特定は出生後に境界明瞭なニッチにおいて生じる(Neuro-immune and inflammatory interaction　Specification of CNS macrophage subsets occurs postnatally in defined niches)

    Masuda Takahiro, Prinz Marco

    日本免疫学会総会・学術集会記録  2022.11  (NPO)日本免疫学会

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    Language：English  

  • 炎症が引き起こす線維化と組織修復　KAI-JSI Joint Session　中枢神経系における多様なマクロファージ(Inflammation driven fibrosis and tissue repair: KAI-JSI Joint Session　Diverse macrophages in the central nervous system)

    Masuda Takahiro

    日本免疫学会総会・学術集会記録  2023.12  (NPO)日本免疫学会

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    Language：English  

  • ミクログリアによる脳情報デコード　ミクログリアのシングルセル解析による脳環境デコーディング(Microglial decoding of brain information　Decoding brain environment through single-cell analysis of microglia)

    Masuda Takahiro

    The Journal of Physiological Sciences  2022.12  (一社)日本生理学会

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MISC

  • Lipid in microglial biology - from material to mediator. Reviewed

    @Yamamoto S, @Masuda T

    Inflammation and Regeneration   2023.7

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    Authorship：Last author,　Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1186/s41232-023-00289-z

  • Mechanisms of myeloid cell entry to the healthy and diseased central nervous system Reviewed International coauthorship

    Amann L, Masuda T, Prinz M

    Nature Immunology   2023.3

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    Authorship：Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Novel insights into the origin and development of CNS macrophage subsets Reviewed International coauthorship

    @Masuda T, Amann L, Prinz M

    Clin Transl Med   2022.11

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    Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Microglia states and nomenclature: A field at its crossroads Reviewed International coauthorship

    Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, Amit I, Audinat E, Bechmann I, Bennett M, Bennett F, Bessis A, Biber K, Bilbo S, Blurton-Jones M, Boddeke E, Brites D, Brône B, Brown GC, Butovsky O, Carson MJ, Castellano B, Colonna M, Cowley SA, Cunningham C, Davalos D, De Jager PL, de Strooper B, Denes A, Eggen BJL, Eyo U, Galea E, Garel S, Ginhoux F, Glass CK, Gokce O, Gomez-Nicola D, González B, Gordon S, Graeber MB, Greenhalgh AD, Gressens P, Greter M, Gutmann DH, Haass C, Heneka MT, Heppner FL, Hong S, Hume DA, Jung S, Kettenmann H, Kipnis J, Koyama R, Lemke G, Lynch M, Majewska A, Malcangio M, Malm T, Mancuso R, Masuda T, Matteoli M, McColl BW, Miron VE, Molofsky AV, Monje M, Mracsko E, Nadjar A, Neher JJ, Neniskyte U, Neumann H, Noda M, Peng B, Peri F, Perry VH, Popovich PG, Pridans C, Priller J, Prinz M, Ragozzino D, Ransohoff RM, Salter MW, Schaefer A, Schafer DP, Schwartz M, Simons M, Smith CJ, Streit WJ, Tay TL, Tsai LH, Verkhratsky A, von Bernhardi R, Wake H, Wittamer V, Wolf SA, Wu LJ, Wyss-Coray T

    Neuron   2022.11

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：Neuron  

    DOI： 10.1016/j.neuron.2022.10.020.

    researchmap

  • Microglia and Central Nervous System-Associated Macrophages-From Origin to Disease Modulation Reviewed International coauthorship

    Prinz M, @Masuda T, Wheeler MA, Quintana FJ

    Annual Review of Immunology   2021.4

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    Authorship：Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1146/annurev-immunol-093019-110159

  • Microglia Heterogeneity in the Single-Cell Era Reviewed International coauthorship

    @Masuda T, Sankowski R, Staszewski O, Prinz M

    Cell Reports   2020.2

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    Authorship：Lead author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1016/j.celrep.2020.01.010.

  • Macrophages at CNS interfaces: ontogeny and function in health and disease Reviewed International coauthorship

    Kierdorf K, @Masuda T, Jordao M, Prinz M

    Nature Reviews Neuroscience   2019.9

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： 10.1038/s41583-019-0201-x

  • 【ヒト疾患と免疫細胞サブセット　解像度をあげて見えてきた病態を規定する疾患のキープレーヤーと治療戦略】(第4章)疾患とのかかわり　ミクログリアの機能と中枢神経系疾患への関与 Invited

    増田 隆博

    実験医学   42 ( 12 )   1944 - 1950   2024.8   （ ISSN:0288-5514 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(株)羊土社  

    脳や脊髄を含む中枢神経系は,全身機能を統括する重要組織であることは疑いようもないが,そのきわめて高度な機能の獲得や維持において欠かすことのできないのが本稿で取りあげるミクログリアである.脳内マクロファージの一種であるミクログリアは,死細胞の除去や組織炎症の制御など典型的な免疫機能のみならず,ほぼすべての脳内生理現象にかかわると考えられている.本稿では,ミクログリアの細胞特性や機能,特に中枢神経系疾患における役割やその機能的多様性について最新の知見を交えながら概説する.(著者抄録)

  • 【グリアは神経回路機能の主役か?】発生期のミクログリアの脳定着機構 Invited

    服部 祐季, 増田 隆博

    細胞   56 ( 8 )   571 - 574   2024.7   （ ISSN:1346-7557 ）

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    Authorship：Last author,　Corresponding author   Language：Japanese   Publisher：(株)ニュー・サイエンス社  

    脳には,神経細胞の他にも免疫系の細胞であるミクログリアが存在し,脳の機能を支えている。成体脳におけるミクログリアの機能解明が進んできた一方,近年,胎生期や生後の脳においてもさまざまな役割を担うことが明らかになりつつある。ミクログリアは,ニューロンや他のグリア細胞とは起源が異なり,卵黄嚢から生じることが知られる。しかし,ミクログリアがいかにして脳に定着するかに関して,その詳細は不明である。最近筆者らは,マウスにおいて脳内のミクログリアは少なくとも二つの異なる定着ルートをたどる細胞集団からなることを見出した。胎生早期にミクログリアの性質を備えて脳に定着を開始する群に加えて,その後遅れて脳室から流入する群が存在することが分かった。本稿では,ミクログリアの脳定着プロセスの解明が性質・機能多様性の理解にどう役立つのかという点にフォーカスし,最新の研究を紹介しながら解説する。(著者抄録)

  • ミクログリアの細胞特性や機能と中枢神経系疾患発症への関与 Invited

    増田 隆博

    臨床免疫・アレルギー科   81 ( 4 )   359 - 365   2024.4   （ ISSN:1881-1930 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(有)科学評論社  

    アストロサイトやオリゴデンドロサイトとともにグリア細胞に分類されるミクログリアは、脳内主要免疫細胞としても知られる脳内マクロファージであり、最近では「神経シナプスの剪定」や「髄鞘形成の促進」といった"免疫"の域にとどまらない機能が数多く報告されている。今回、ミクログリアの発生維持メカニズムや細胞特性、細胞機能、中枢神経疾患への関与などについて、これまでの知見を以下の項目に分けて概説した。1)ミクログリアの発生と脳内定着・維持。2)ミクログリアと脳境界マクロファージ。3)ミクログリアのアルツハイマー病への関与。4)多発性硬化症への関与。5)腸内細菌叢によるミクログリア機能の制御。

  • 脳内マクロファージの統合的理解に向けた研究 Invited

    増田 隆博

    神経化学   62 ( 2 )   38 - 41   2023.12   （ ISSN:0037-3796 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publisher：(一社)日本神経化学会  

  • 中枢神経系マクロファージをめぐる新展開　ミクログリア・脳境界マクロファージの分化,特性 Invited

    増田 隆博

    感染・炎症・免疫   53 ( 2 )   98 - 106   2023.10   （ ISSN:0387-1010 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：鳥居薬品(株)  

    脳と脊髄で構成される中枢神経系が全身機能を司る重要組織であることは周知の事実であるが,その組織環境や機能を維持するために欠かすことのできない存在として知られるのが中枢神経系マクロファージである.中枢神経系マクロファージは,分布領域の違いから,実質内に存在するミクログリアと,髄膜や血管周囲スペースなどの境界領域に存在する脳境界マクロファージに大別される.ミクログリアは死細胞の除去やシナプス剪定などさまざまな機能を担うことが明らかになっている一方で,脳境界マクロファージの存在意義や細胞特性にはいまだ不明な点が多く,またミクログリアと脳境界マクロファージを正確に分けて解析した報告も少ない.そのようななか,近年の研究技術の進歩や研究ツールの開発に伴って,両細胞種の分離機能解析が可能になってきた.本稿では,ミクログリアと脳境界マクロファージの細胞特性や機能に関して,最新の知見を交えて概説する.(著者抄録)

  • 【ミエロイド系細胞の新時代:発生機構から創薬標的としての可能性まで】正常時および病態時における中枢神経系マクロファージの多様性 Invited

    増田 隆博

    日本薬理学雑誌   158 ( 4 )   308 - 311   2023.7   （ ISSN:0015-5691 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(公社)日本薬理学会  

    脳および脊髄を含む中枢神経系組織は,神経細胞やグリア細胞,血管系細胞や免疫細胞など多種多様な細胞によって構成され,それらの複雑かつダイナミックな相互作用によって高度な機能が維持されている.その中でも,中枢機能を正確に維持するために欠かすことのできない細胞が,著者らの研究対象である脳内マクロファージである.脳内マクロファージと聞いてまず思い浮かぶのが,脳内主要免疫細胞として知られるミクログリアではないかと思う.長年の研究から,ミクログリアの細胞特性や機能,他の免疫細胞との関係,中枢神経系疾患への関与などが明らかになってきている.一方,ミクログリアの傍らであまり目を向けられてこなかった第2の脳内マクロファージが存在する.それが,髄膜や血管周囲空間などの境界領域に存在する脳境界マクロファージ(CNS associated macrophages:CAMs)である.その存在は長年認知されてきたものの,CAMsはミクログリアと遺伝子プロファイルが非常に似ており,これまで両細胞種を正確に分けて解析した報告は少なかった.近年,CAMsに着目した研究も増加しつつあり,その理解もようやく進み始めた.本稿では,ミクログリアおよびCAMsに関して,その発生・維持メカニズムや細胞特性,またそれらを解析するための研究ツールについて,最新の知見を交えて概説する.(著者抄録)

  • ミクログリア生物学における脂質　材料からメディエーターへ(Lipid in microglial biology: from material to mediator)

    Yamamoto Shota, Masuda Takahiro

    Inflammation and Regeneration   43   1 of 6 - 6 of 6   2023.7   （ ISSN:1880-9693 ）

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    Language：English   Publisher：(一社)日本炎症・再生医学会  

  • Central Nervous System Tumor　脳腫瘍　脳腫瘍と免疫システムUpdate　脳境界マクロファージと脳免疫システム Invited

    増田 隆博

    癌と化学療法   50 ( 6 )   690 - 693   2023.6   （ ISSN:0385-0684 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(株)癌と化学療法社  

  • Microglial diversity in neuropathic pain Reviewed

    Tsuda M, Masuda T, Kohno K

    Trends in Neuroscience   2023.5

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • 中枢神経系のマクロファージに関する最近の話題(Recent topics regarding macrophage in the central nervous system) Invited Reviewed

    Masuda Takahiro

    The Journal of Biochemistry   173 ( 3 )   139 - 143   2023.3   （ ISSN:0021-924X ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：(公社)日本生化学会  

  • 【間質リテラシーと疾患】中枢神経系の間質に常在する脳内マクロファージと疾患 Invited

    増田 隆博

    炎症と免疫   31 ( 1 )   3 - 6   2022.12   （ ISSN:0918-8371 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(株)先端医学社  

    脳や脊髄を含む中枢神経系は,無数に張り巡らされた神経細胞を基本骨格とした複雑な構造体である.その間質領域は,免疫細胞やグリア細胞,血管系細胞など多様な細胞によって満たされているが,それらは単なる組織の支持細胞ではなく,複雑かつダイナミックな相互作用を介して中枢神経系の高度な機能発現に積極的に関与している.本稿では,中枢神経系の間質における主要免疫細胞として知られる脳内マクロファージのうち,とくにミクログリアの細胞特性や疾患発症への関与について,最新の知見を交えて概説する.(著者抄録)

  • 精神科医に知ってもらいたい医学生物学の先端技術　一細胞解析が切り開く医学生物学研究 Invited

    増田 隆博

    臨床精神医学   51 ( 12 )   1441 - 1443   2022.12   （ ISSN:0300-032X ）

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  • Recent topics regarding macrophage in the central nervous system Reviewed

    @Masuda T

    Journal of Biochemistry   2022.11

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  • 【脳をしなやかに制御するミクログリアと脳内免疫系　見えてきた起源と多様性、創薬標的の可能性】脳実質ミクログリアと脳境界マクロファージ Invited

    増田 隆博

    実験医学   40 ( 18 )   2961 - 2966   2022.11   （ ISSN:0288-5514 ）

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    Authorship：Lead author,　Last author,　Corresponding author   Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (trade magazine, newspaper, online media)   Publisher：(株)羊土社  

    中枢神経系を構成する主要免疫細胞として君臨するミクログリアの傍らで,あまり目を向けられてこなかった第2の脳内マクロファージが存在する.それが,脳境界マクロファージ(CNS associated macrophages, CAMs)である.その存在は数十年前から認知されていたにもかかわらず,これまでミクログリアとCAMsを正確に分けて解析した報告は少ない.しかし,近年の研究技術の進歩に伴って,CAMsに着目した研究も増加しつつあり,その理解も進み始めた.本稿では,これまで明らかになっているCAMsの細胞特性や機能に関して,特にミクログリアとの類似・相違点という観点から概説する.(著者抄録)

  • Author Correction: Specification of CNS macrophage subsets occurs postnatally in defined niches (Nature, (2022), 604, 7907, (740-748), 10.1038/s41586-022-04596-2) Reviewed International coauthorship

    Masuda T., Amann L., Monaco G., Sankowski R., Staszewski O., Krueger M., Del Gaudio F., He L., Paterson N., Nent E., Fernández-Klett F., Yamasaki A., Frosch M., Fliegauf M., Bosch L.F.P., Ulupinar H., Hagemeyer N., Schreiner D., Dorrier C., Tsuda M., Grothe C., Joutel A., Daneman R., Betsholtz C., Lendahl U., Knobeloch K.P., Lämmermann T., Priller J., Kierdorf K., Prinz M.

    Nature   610 ( 7930 )   E1   2022.10   （ ISSN:00280836 ）

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    Language：English   Publisher：Nature  

    In the version of this article initially published online, there was a copy– paste duplication of values in the source data for Figure 1b, Parenchyma: Cx3cr1-GFP+. The correct values have been restored in the HTML version of this article.

    DOI： 10.1038/s41586-022-05361-1

    Scopus

    PubMed

  • 【マクロファージの多様性】多様な脳内マクロファージからみる正常脳と中枢神経系疾患 Invited

    増田 隆博

    臨床免疫・アレルギー科   78 ( 2 )   155 - 161   2022.8   （ ISSN:1881-1930 ）

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  • Author Correction: Mapping microglia states in the human brain through the integration of high-dimensional techniques (Nature Neuroscience, (2019), 22, 12, (2098-2110), 10.1038/s41593-019-0532-y) Reviewed International coauthorship

    Sankowski R., Böttcher C., Masuda T., Geirsdottir L., Sagar , Sindram E., Seredenina T., Muhs A., Scheiwe C., Shah M.J., Heiland D.H., Schnell O., Grün D., Priller J., Prinz M.

    Nature Neuroscience   25 ( 7 )   2022.7   （ ISSN:10976256 ）

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)   Publisher：Nature Neuroscience  

    In the version of this article initially published, Fig.3b,c, Fig. 5a–d, Extended Data Fig. 1 and Supplementary Fig. 8b contained errors. Fig. 3b and c showed incorrect immunohistochemistry quantifications. Fig. 5a contained a duplicate image for the TMEM119 control sample, and panels b and c showed incorrect immunohistochemistry quantifications. Fig. 5d contained an incorrect image for the t-SNE map of P2RY12; it was a duplicate of the map for HLA-DRA. Extended Data Fig. 1 contained incorrect images in panel a for Pat 7 (TMEM119), Pat 12 (TMEM119, CD74) and Pat 15 (CD68) and in panel b for Pat 3 (GFAP), Pat 12 (TMEM119 and P2YR12) and Pat 13 (TMEM119). Supplementary Fig. 8b contained an incorrect image for the CSF2 t-SNE panel. In addition, the legend for Fig. 5b as well as the description of Fig. 1b in Methods incorrectly said that the test used was a paired t-test; it should read ‘unpaired t-test’ in both places. In the Results section, the sentence “Normalization for the number of IBA1+ cells revealed lower expression of the bona fide microglial markers P2RY12 and TMEM119, and higher expression of HLA-DR (Fig. 5c)” should read “no change of expression” instead of “lower expression”. The errors have been corrected in the HTML and PDF versions of the article.

    DOI： 10.1038/s41593-022-01089-3

    Scopus

  • 脳内免疫細胞ミクログリアの時空間的多様性 Reviewed

    @増田隆博

    神経化学トピックス   2019.6

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    Language：Japanese   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： DOI: 10.11481/topics107

  • Microglia: A Unique Versatile Cell in the Central Nervous System Reviewed

    @Masuda T, Prinz M

    ACS Chemical Neuroscience   2016.4

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

    DOI： DOI: 10.1021/acschemneuro.5b00317

  • Transcriptional regulation in microglia and neuropathic pain Reviewed

    @Masuda T, @Tsuda M, @Inoue K

    Pain Management   2016.4

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • P2X4 receptors and neuropathic pain

    Makoto Tsuda, Takahiro Masuda, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue

    Front Cell Neurosci.   2013.10

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

  • Microglial regulation of neuropathic pain

    Makoto Tsuda, Takahiro Masuda, Hidetoshi Tozaki-Saitoh, Kazuhide Inoue

    Journal of Pharmacological Sciences   2013.1

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    Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

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Professional Memberships

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Academic Activities

  • Screening of academic papers

    Role(s)： Peer review

    2023

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：13

    Number of peer-reviewed articles in Japanese journals：0

    Proceedings of International Conference Number of peer-reviewed papers：0

    Proceedings of domestic conference Number of peer-reviewed papers：0

  • Screening of academic papers

    Role(s)： Peer review

    2022

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：13

    Number of peer-reviewed articles in Japanese journals：0

    Proceedings of International Conference Number of peer-reviewed papers：0

    Proceedings of domestic conference Number of peer-reviewed papers：0

  • Screening of academic papers

    Role(s)： Peer review

    2021

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：11

    Number of peer-reviewed articles in Japanese journals：0

    Proceedings of International Conference Number of peer-reviewed papers：0

    Proceedings of domestic conference Number of peer-reviewed papers：0

  • Frontiers in Cellular Neuroscience International contribution

    2020.9 - 2021.6

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    Type：Academic society, research group, etc. 

  • Screening of academic papers

    Role(s)： Peer review

    2020

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    Type：Peer review 

    Number of peer-reviewed articles in foreign language journals：16

    Number of peer-reviewed articles in Japanese journals：0

    Proceedings of International Conference Number of peer-reviewed papers：0

    Proceedings of domestic conference Number of peer-reviewed papers：0

Research Projects

  • 令和6年度日本人独立研究者始動助成金/脳境界構成細胞を標的とした新規疾患制御ストラテジーの探索

    2024

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    Grant type：Donation

  • 2023年度研究助成金/脳境界領域を取り巻く細胞群による脳機能制御メカニズムの解明と機能的介入法の確立

    2024

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    Grant type：Donation

  • 脳内マクロファージの多様性と中枢神経系疾患

    2023 - 2030

    創発的研究支援事業

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    Authorship：Principal investigator  Grant type：Contract research

  • グリア細胞の生理機構解明とその遷移による中枢神経疾患に対する創薬戦略の国際共同開発

    2023 - 2028

    AMED 医療分野国際科学技術共同研究開発推進事業（先端国際共同研究推進プログラムASPIRE）

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    Authorship：Coinvestigator(s)  Grant type：Contract research

  • 非神経細胞のストレスエングラムから読み解く心的フレイルの統合的理解と診断的治療への応用

    2023 - 2028

    革新的先端研究開発支援事業(AMED-CREST)

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    Authorship：Principal investigator  Grant type：Contract research

  • Elucidation of Mechanisms of the Centenarian Dynamic Resilience through Immune Systems

    2023 - 2027

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    Authorship：Coinvestigator(s)  Grant type：Contract research

  • 2023年度研究助成金/脳境界構成細胞を標的とした疾患発症メカニズムの統合的理解

    2023

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    Grant type：Donation

  • 2023年度 ビジョナリーリサーチ継続助成（ホップ）/脳内マクロファージサブタイプの機能分離解析に基づく中枢神経系疾患発症メカニズムの理解と新規治療法の創出

    2023

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    Grant type：Donation

  • ＰＩセットアップ研究助成/脳内マクロファージを切り口とした中枢神経系疾患発症メカニズムの理解

    2023

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    Grant type：Donation

  • 2023 年度助成金/中枢性疾患に関わる脳内マクロファージの統合的理解

    2023

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    Grant type：Donation

  • 2023年度持田記念研究助成金/脳境界免疫を基軸とした中枢性疾患発症メカニズムの理解

    2023

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    Grant type：Donation

  • 2023年度 研究助成⾦/脳境界マクロファージによる疾患制御メカニズムの解明

    2023

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    Grant type：Donation

  • Establishment of interstitial literacy based on complex systems crosstalk

    Grant number：22H05060  2022.5 - 2025.3

    Grants-in-Aid for Scientific Research  Grant-in-Aid for Transformative Research Areas (B)

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    Grant type：Scientific research funding

    CiNii Research

  • 神経系疾患発症に紐づく間質性細胞間クロストークの包括的理解

    Grant number：22H05062  2022 - 2024

    日本学術振興会・文部科学省  科学研究費助成事業  学術変革領域研究(B)

    増田 隆博, 石亀 晴道

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    Authorship：Principal investigator  Grant type：Scientific research funding

    本研究では神経系を構成する間質性細胞を包括的に解析し、実質細胞の機能異常に紐づく間質組織変容の解明を進める（神経系間質リテラシー）。特に様々な最新技術を駆使し、脳発達期における間質性細胞ネットワークの理解を進め、その異常がもたらす疾患発症メカニズムの解明を目指すと同時に、中枢神経系疾患モデルマウスを用いて、複雑性間質性細胞クロストークが齎す実質細胞の機能変容という観点から新たな疾患発症メカニズムの解明を目指す。

    CiNii Research

  • 新規細胞機能操作ツールを用いた中枢性疾患発症メカニズムの理解

    Grant number：23K21383  2021.4 - 2025.3

    科学研究費助成事業  基盤研究(B)

    増田 隆博

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    Grant type：Scientific research funding

    本研究計画は、中枢神経系疾患発症における脳境界マクロファージの存在意義に迫るという、これまで全く未開拓の研究領域である。そのため、本研究課題で得られた成果は脳境界マクロファージが持つ生理機能の全貌解明に大きく貢献することが予想される。また、それらはアルツハイマー病や多発性硬化症などの脳神経・免疫疾患の発症メカニズムの解明および治療法開発にも波及的に貢献する可能性があると考えられ、新たな”ドラッガブル”な細胞標的の創出につながることも期待される。

    CiNii Research

  • 新規細胞機能操作ツールを用いた中枢性疾患発症メカニズムの理解

    Grant number：21H02752  2021 - 2024

    日本学術振興会  科学研究費助成事業  基盤研究(B)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 慢性ストレス・老化による脳機能変容の炎症性機序の解明

    2021 - 2024

    AMED 脳とこころの研究推進プログラム（精神・神経疾患メカニズム解明プロジェクト）

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    Authorship：Coinvestigator(s)  Grant type：Contract research

  • 精神疾患発症における脳内免疫細胞CAMsの可能性

    Grant number：21H00204  2021 - 2022

    日本学術振興会・文部科学省  科学研究費助成事業  新学術領域研究（研究領域提案型）

    増田 隆博

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    Authorship：Principal investigator  Grant type：Scientific research funding

    本研究課題で得られた成果は、CAMs が持つ生理機能の全貌解明に大きく貢献することが予想され、またCAMs の異常活性化や機能不全が齎す新たな中枢神経系疾患”CAMs 病”の発見に繋がる可能性もあり、精神疾患に対する新たな”ドラッガブル”な細胞標的の創出につながることも期待される。

    CiNii Research

  • 稲盛研究助成/脳境界マクロファージの包括的解析から見る正常脳形成と中枢性疾患発症

    2021

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    Grant type：Donation

  • 武田科学振興財団　ビジョナリーリサーチ助成（スタート）/　脳内マクロファージサブタイプの機能分離解析に基づく中枢神経系疾患発症メカニズムの理解と新規治療法の創出

    2021

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    Grant type：Donation

  • 早期ライフステージの脳内免疫細胞から紐解く正常脳形成と中枢性疾患発症

    2020 - 2023

    革新的先端研究開発支援事業（AMED-PRIME）

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    Authorship：Principal investigator  Grant type：Contract research

  • 中枢神経系マクロファージの機能解明を目的とした新規研究基盤の創出

    Grant number：20K22687  2020 - 2021

    日本学術振興会  科学研究費助成事業  研究活動スタート支援

    増田 隆博

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    Authorship：Principal investigator  Grant type：Scientific research funding

    脳および脊髄を含む中枢神経系組織には、実質に存在するミクログリア細胞に加え、境界領域に種類の異なるマクロファージ[CNS-associated macrophages(CAMs)]が存在する。本研究では、以下２項目 (１) シングルセルトランスクリプトーム解析技術を用いたミクログリアおよびCAMsの遺伝子発現プロファイルの包括的比較解析によるミクログリア特異的遺伝子の特定、 (2) ミクログリア特異的遺伝子のプロモーターを用いた細胞種特異的遺伝子改変マウスの作成およびその機能解析を進め、ミクログリアおよびCAMsの機能解明に向けた研究基盤の創出を目指す。

    CiNii Research

  • 内藤記念科学奨励金　研究助成/ 新規機能操作ツールを用いた各種脳内マクロファージの存在意義の理解

    2020

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    Grant type：Donation

  • 研究助成金/ 脳内マクロファージの機能解明に向けた基盤情報および新規ツールの創出

    2020

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    Grant type：Donation

  • ミクログリア前駆細胞の脳内定着メカニズムの解明

    2015 - 2017

    日本学術振興会  海外特別研究員

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    Authorship：Principal investigator  Grant type：Joint research

  • 海外留学助成金/中枢神経系組織におけるミクログリア細胞の不均一性

    2015

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    Grant type：Donation

  • IRFとターゲットとしたミクログリアによる神経障害性疼痛発現メカニズムの解明

    Grant number：23890148  2011 - 2012

    科学研究費助成事業  若手研究(スタートアップ)

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    Authorship：Principal investigator  Grant type：Scientific research funding

  • 神​経​因​性​疼​痛​に​お​け​る​I​F​N​-​γ​を​介​し​た​ミ​ク​ロ​グ​リ​ア​の​活​性​化​機​構

    Grant number：20・5285  2008 - 2010

    日本学術振興会  科学研究費助成事業  特別研究員奨励費

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    Authorship：Principal investigator  Grant type：Scientific research funding

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Class subject

  • 医学研究特論Ⅰ

    2023.4 - 2024.3   Full year

  • アカデミック・フロンティアⅠ

    2023.4 - 2023.6   Spring quarter

  • 薬理・基礎理論

    2022.10 - 2023.3   Second semester

  • 基幹教育セミナー

    2022.6 - 2022.8   Summer quarter

FD Participation

  • 2024.4   Role：Participation   Title：職場における落とし穴

    Organizer：[Undergraduate school/graduate school/graduate faculty]

  • 2022.4   Role：Participation   Title：学生の多様性に対応した教育とは：障害学生への合理的配慮を中心に

    Organizer：[Undergraduate school/graduate school/graduate faculty]

  • 2021.9   Role：Participation   Title：JST 次世代研究者挑戦的研究プログラム 説明会

    Organizer：University-wide

  • 2021.9   Role：Participation   Title：M2B学習支援システム講習会★初級・中上級編★

    Organizer：University-wide

  • 2021.7   Role：Participation   Title：生体防御医学研究所FD

    Organizer：[Undergraduate school/graduate school/graduate faculty]

  • 2021.4   Role：Participation   Title：令和３年度 第１回全学ＦＤ（新任教員の研修）

    Organizer：University-wide

  • 2021.2   Role：Participation   Title：創薬産学官連携セミナー

    Organizer：[Undergraduate school/graduate school/graduate faculty]

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Other educational activity and Special note

  • 2022  Class Teacher