| Takashi Maehara | Last modified date：2024.04.09 |
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Homepage
https://kyushu-u.elsevierpure.com/en/persons/takashi-maehara
Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-6447
Fax
092-642-6386
Academic Degree
Doctor of Dental Science, Doctor of Philosophy
Country of degree conferring institution (Overseas)
Yes
Field of Specialization
Section of Oral and Maxillofacial Oncology Division of Maxillofacial Diagnostic and Surgical Sciences Faculty of Dental Science,Kyushu University
Total Priod of education and research career in the foreign country
03years00months
Research
Research Interests
Membership in Academic Society
- International joint research for Systemic sclerosis
keyword : systemic sclerosis, SSc
2017.01～2020.12. - International joint research、IgG4-related disease
keyword : IgG4-related disease
2018.07～2022.07. - Oral lichen planus
keyword : Oral Lichen Planus、Th subsets
2016.04～2018.12. - IgG4-related disease
keyword : International joint research、IgG4-related disease
2018.04～2018.12. - IgG4-related disease
keyword : IgG4-related disease、ectopic germinal center、Th cell
2014.04～2016.03. - Perform further Tossue FAXS studies on T cell subsets and repertoire in IgG4-RD and other diseases including SS also examining mechanism of fibrosis, before and after Rituximab Therapy
keyword : Tissue FAXS、T cell subsets、IgG4-related disease、SS、Rituximab
2015.03～2016.03. - New analysis of pathogenesis of IgG4-related disease - Th cells and Type 2 Innate lymphoid cells -
keyword : CD4+T cells, B cells, Th2, CD4+CTL, Tfh
2016.04～2018.03.
Papers
| 1. | Risako Koga, Takashi Maehara, Ryuichi Aoyagi, Ryusuke Munemura, Yuka Murakami, Atsushi Doi, Michihito Kono, Hidetaka Yamamoto, Hiroaki Niiro, Tamotsu Kiyoshima, Mika Tanabe, Toshiaki Nakano, Yuta Matsukuma, Mitsuhiro Kawano, John H Stone, Shiv Pillai, Seiji Nakamura, Shintaro Kawano , Granzyme K- and amphiregulin-expressing cytotoxic T cells and activated extrafollicular B cells are potential drivers of IgG4-related disease , J Allergy Clin Immunol, 10.1016/j.jaci.2023.11.916, 2023.12. |
| 2. | Ryuichi Aoyagi, Takashi Maehara, Risako Koga, Ryusuke Munemura, Tadashi Tomonaga, Yuka Murakami, Atsushi Doi, Hidetaka Yamamoto , Tamotsu Kiyoshima, Shintaro Kawano, Seiji Nakamura , Single-cell transcriptomics reveals granzyme K-expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD, J Allergy Clin Immunol, 10.1016/j.jaci.2023.08.019, 2023.08. |
| 3. | Maehara T, Koga R, Nakamura S., Immune dysregulation in immunoglobulin G4-related disease., Jpn Dent Sci Rev., 2023.06. |
| 4. | Ryusuke Munemura, TAKASHI MAEHARA, Yuka Murakami, Risako Koga, Ryuichi Aoyagi, Naoki Kaneko, Atsushi Doi, Cory A. Perugino, Emanuel Della-Torre, Takako Saeki, Yasuharu Sato, Hidetaka Yamamoto, Tamotsu Kiyoshima, John H. Stone, Shiv Pillai, Seiji Nakamura., Distinct disease-specific Tfh cell populations in two different fibrotic diseases: IgG4- related disease and Kimura’s disease, The Journal of Allergy and Clinical Immunology, doi: 10.1016/j.jaci.2022.03.034., 2022.04, Background: How T follicular (Tfh) cells contribute to many different B-cell class-switching events during T-cell–dependent immune responses has been unclear. Diseases with polarized isotype switching offer a unique opportunity for the exploration of Tfh subsets. Secondary and tertiary lymphoid organs in patients with elevated tissue expression levels of IgE (Kimura disease, KD) and those of IgG4 (IgG4-related disease, IgG4-RD) can provide important insights regarding cytokine expression by Tfh cells. Objective: We sought to identify disease-specific Tfh cell subsets in secondary and tertiary lymphoid organs expressing IL-10 or IL-13 and thus identify different cellular drivers of class switching in 2 distinct types of fibrotic disorders: allergic fibrosis (driven by type 2 immune cells) and inflammatory fibrosis (driven by cytotoxic T lymphocytes). Methods: Single-cell RNA sequencing, in situ sequencing, and multicolor immunofluorescence analysis were used to investigate B cells, Tfh cells, and infiltrating type 2 cells in lesion tissues from patients with KD or IgG4-RD. Results: Infiltrating Tfh cells in tertiary lymphoid organs from IgG4-RD were divided into 6 main clusters. We encountered abundant infiltrating IL-10–expressing LAG31 Tfh cells in patients with IgG4-RD. Furthermore, we found that infiltrating AICDA1CD191 B cells expressing IL-4, IL-10, and IL-21 receptors correlated with IgG4 expression. In contrast, we found that infiltrating IL-13–expressing Tfh cells were abundant in affected tissues from patients with KD. Moreover, we observed few infiltrating IL-13–expressing Tfh cells in tissues from patients with IgG4-RD, despite high serum levels of IgE (but low IgE in the disease lesions). Cytotoxic T cells were abundant in IgG4-RD; in contrast, type 2 immune cells were abundant in KD. Conclusions: Our analysis revealed a novel subset of IL-101LAG31 Tfh cells infiltrating the affected organs of IgG4-RD patients. In contrast, IL-131 Tfh cells and type 2 immune cells infiltrated those of KD patients. (J Allergy Clin Immunol 2022;150:440-55.). |
| 5. | Cory A. Perugino, Naoki Kaneko, Takashi Maehara, Hamid Mattoo, Jesper Kers, Hugues Allard-Chamard, Vinay S. Mahajan, Hang Liu, Emanuel Della-Torre, Samuel JH. Murphy, Musie Ghebremichael, Zachary S. Wallace, Geetha Mylvaganam, Yesim Tuncay, Lloyd Liang, Sydney B. Montesi, Akira Tinju, Keita Mochizuki, Ryusuke Munemura, Mizuki Sakamoto, Masafumi Moriyama, Seiji Nakamura, Nir Yosef,John H. Stone, Shiv Pillai, CD4+ and CD8+ cytotoxic T lymphocytes may induce mesenchymal cell apoptosis in IgG4-related disease, J Allergy Clin Immunol, 2020.05. |
| 6. | Takashi Maehara, Naoki Kaneko, Cory A. Perugino, Hamid Mattoo, Jesper Kers, Hugues Allard-Chamard, Vinay S. Mahajan, Hang Liu, Samuel J.H. Murphy, Musie Ghebremichael, David Fox, Aimee S. Payne, Robert Lafyatis, John H. Stone, Dinesh Khanna, Shiv Pillai, Cytotoxic CD4+ T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis, Journal of Clinical Investigation, 10.1172/JCI131700, 130, 5, 2451-2464, 2020.05, Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4+ cytotoxic T cells and CD8+ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR-expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4+ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.. |
| 7. | Takashi Maehara, Masafumi Moriyama, Seiji Nakamura, A novel disease entity IgG4-related disease, including so-called Mikulicz's disease and Kuttner's tumor, KAOMS, 2020.01. |
| 8. | Claudia Minici, Elena Rigamonti, Marco Lanzillotta, Antonella Monno, Lucrezia Rovati, Takashi Maehara, Naoki Kaneko, Vikram Deshpande, Maria Pia Protti, Lucia De Monte, Cristina Scielzo, Stefano Crippa, Paolo Giorgio Arcidiacono, Erica Dugnani, Lorenzo Piemonti, Massimo Falconi, Shiv Pillai, Angelo A. Manfredi, Emanuel Della-Torre, B lymphocytes contribute to stromal reaction in pancreatic ductal adenocarcinoma, OncoImmunology, 10.1080/2162402X.2020.1794359, 9, 1, 2020.01, Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent stromal reaction that has been variably implicated in both tumor growth and tumor suppression. B-lymphocytes have been recently implicated in PDAC progression but their contribution to the characteristic stromal desmoplasia has never been assessed before. In the present work, we aimed to verify whether B-lymphocytes contribute to stromal cell activation in PDAC. CD19+ B-lymphocytes purified from peripheral blood of patients with PDAC were cultivated in the presence of human pancreatic fibroblasts and cancer-associated fibroblasts. Released pro-fibrotic soluble factors and collagen production were assessed by ELISA and Luminex assays. Quantitative RT-PCR was used to assess fibroblast activation in the presence of B cells. The expression of selected pro-fibrotic and inflammatory molecules was confirmed on PDAC tissue sections by multi-color immunofluorescence studies. We herein demonstrate that B-cells from PDAC patients (i) produce the pro-fibrotic molecule PDGF-B and stimulate collagen production by fibroblasts; (ii) express enzymes implicated in extracellular matrix remodeling including LOXL2; and (iii) produce the chemotactic factors CCL-4, CCL-5, and CCL-11. In addition we demonstrate that circulating plasmablasts are expanded in the peripheral blood of patients with PDAC, stimulate collagen production by fibroblasts, and infiltrate pancreatic lesions. Our results indicate that PDAC is characterized by perturbations of the B-cell compartment with expansion of B-lymphocyte subsets that directly contribute to the stromal reaction observed at disease site. These findings provide an additional rationale for modulating B-cell activity in patients with pancreatic cancer.. |
| 9. | Takashi Maehara, Naoki Kaneko, Cory A Perugino, Hamid Matteo, Jesper Kers, Hugues Allard-Chamard, Vinay S Mahajan, Hang Liu, Samuel JH Murphy, Musie Ghebremichael, David Fox, Rovert Lafyatis, John H. Stone, Dinesh Khanna, Shiv Pillai., Cytotoxic CD4+T lymphocytes may induce endothelial cell apoptosis in systemic sclerosis, Journal of Clinical Investigation, 2019.12. |
| 10. | Takashi Maehara, Ryusuke Minemura, Mayumi Shimizu, Noriko Kakizoe, Naoki Kaneko, Moriyama Masafumi, Yuka Murakami, Tamotsu Kiyoshima, Shintaro Kawano, Seiji Nakamura., Tissue-infiltrating immune cells contribute to understanding the pathogenesis of Kimura's Disease: a case report, Medicine, 2019.11. |
| 11. | Della-Torre E, Rigamonti E, Perugino C, Sain SB, Sun N, Kaneko N, Maehara T, Rovati L, Ponzoni M, Milani R, Lanzillotta M, Mahajan V, Mattoo H, Molineris I, Deshpande V, Stone JH, Falconi M, Manfredi AA, Pillai S., B lymphocytes directly contribute to tissue fibrosis in IgG4-Related Disease., J Allergy Clin Immunol, 10.1016/j.jaci.2019.07.004, 2019.07. |
| 12. | Takashi Maehara, Yuka Murakami, Shintaro Kawano, Yurie Mikami, Tamotsu Kiyoshima, Toru Chikui, Noriko Kakizoe, Ryusuke Munemura, Seiji Nakamura, Osteoid osteoma of mandibular bone: Case report and review of the literature, Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 2019.04. |
| 13. | Takashi Maehara, Shiv Pillai, John H Stone, and Seiji Nakamura, Clinical Features and Mechanistic Insights Regarding IgG4-Related Dacryoadenitis and Sialoadenitis: a review, International Journal of Oral & Maxillofacial Surgery , 2018.11. |
| 14. | Julia Roider1, TAKASHI MAEHARA2, Abgail Ngoepe3, Duran Ramsuran3, Maximilian Münchhoff4, Emily Adland5, Toby Aicher6, Samuel Kazer6, Pieter Jooste7, Farina Karim3, Warren Kuhn8, Alex Shalek6, Thumbi Ndung'u3, Lynn Morris9, Penny Moore9, Shiv Pillai2, Henrik Kloverpris3, Philip Goulder5* and Alasdair Leslie, High-frequency, functional HIV-specific T-follicular helper and regulatory cells are present within germinal centers in children but not adults., Frontiers in Immunology, 2018.08. |
| 15. | Maehara T, Moriyama M, Nakamura S., Pathogenesis of IgG4-related disease: a critical review., Odontology, doi: 10.1007/s10266-018-0377-y., 2018.07. |
| 16. | Maehara T, Mattoo H, Mahajan V, Murphy S, Yuen G, Ishiguro N, Ohta M, Moriyama M, Saeki T, Yamamoto H, Yamauchi M, Daccache J, Kiyoshima T, Nakamura S, Stone JH, Pillai S., The expansion in lymphoid organs of IL-4+BATF+T follicular helper cells is linked to IgG4 class switching in vivo., Life Science Alliance., 10.26508/lsa.201800050, 2018.04, [URL]. |
| 17. | Perugino CA, Matto H, Mahajan VS, Maehara T, Wallace ZS, Pillai S, Stone JH., IgG4-related disease: Insights into human immunology and targeted therapies., Arthritis Rheumatol. 2017 Sep;69(9):1722-1732., 2017.09. |
| 18. | Maehara Takashi., IgG4-related disease –Mechanistic insights from both clinical and immunologic understanding of this condition., The Japan Society for Clinical Immunology. 2017;40(3):206-212., 2017.05. |
| 19. | Maehara T, Mattoo H, Ohta M, Mahajan V, Moriyama M, Yamauchi M, Drijvers S, Nakamura S, Stone JH, Pillai S., Lesional CD4+IFN-gamma+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoadenitis., Ann. Rheum. Dis. 2017 Feb;76(2):377-385., 2017.02. |
| 20. | Matoo H, Mahajan V, Maehara T, Deshpande V, Della-Torre E, Wallace ZS, Kulikova M, Drijvers S, Daccache J, Carruthers MN, Castelino FV, Stone JR, Stone JH, Pillai S., Clonal expansion of CD4+ cytotoxic T lymphocytes in patients with IgG4-related disease., J Allergy Clin Immunol. 2016 Sep;138(3):825-38., 2016.09. |
| 21. | Maehara T, Moriyama M, Nakashima H, Miyake K, Hayashida JN, Tanaka A, Shinozaki S, Kubo Y, Nakamura S., Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz’s disease., Ann. Rheum. Dis. 2012 Dec;71(12):2011-19., 2012.12. |
| 22. | Takashi Maehara, Masafumi Moriyama, Hitoshi Nakashima, Katsuhisa Miyake, Jun Nosuke Hayashida, Akihiko Tanaka, Shouichi Shinozaki, Yoshiaki Kubo, Seiji Nakamura, Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacryoadenitis and sialoadenitis, so-called Mikulicz's disease, Annals of the Rheumatic Diseases, 10.1136/annrheumdis-2012-201477, 71, 12, 2011-2019, 2012.12, Objectives: Interleukin (IL)-21 is mainly produced by CD4 T helper (Th) cells including Th2, Th17 and follicular helper T (Tfh) cells. Recent studies have reported that IL-21 is involved in the formation of germinal centres (GCs) and class switching of IgG4. It has been suggested that IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS), so-called Mikulicz's disease (MD), is distinct from Sjögren's syndrome (SS) and shows a high frequency of GC formation in salivary glands. In this study the expression of IL-21 in IgG4-DS and SS patients was examined. Methods: Twelve patients with IgG4-DS, 15 with SS and 15 healthy subjects were screened for (1) ectopic GC formation in formalin-fixed labial salivary gland (LSG) biopsy samples; (2) expression of IL-21, Th2-, Th17- and Tfh-related molecules (cytokines, chemokine receptors and transcription factors) in LSGs; (3) relationship between IgG4/IgG ratio and mRNA expression of IL-21 in LSGs. Results: mRNA expression of IL-21 and Bcl-6 in LSGs from patients with IgG4-DS was significantly higher than in patients with SS and controls. IL-21 and CXCR5 were detected by immunohistochemistry in or around GC in patients with SS and those with IgG4-DS. IL-21 was detected in infiltrating lymphocytes outside GC only in patients with IgG4-DS. Expression of IL-21 was consistent with that of Th2-related molecules while IL-17 was rarely seen in IgG4-DS. Furthermore, the expression of IL-21 in LSGs was correlated with the number of GC formations and the IgG4/IgG ratio in patients with IgG4-DS. Conclusions: These results suggest that overexpression of IL-21 by Th2 cells might play a key role in GC formation and IgG4 production in IgG4-DS.. |
| 23. | Maehara T, Moriyama M, Hayashida JN, Tanaka A, Shinozaki S, Kubo Y, Matsumura K, Nakamura S., Selective localization of T helper subsets in labial salivary glands from primary Sjogren’s syndrome patietns., Clin Exp Immunol. 2012 Aug;169(2):89-99., 2012.08. |
Presentations
- International Association of Dental Research
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