Kyushu University Academic Staff Educational and Research Activities Database
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Maehara Takashi Last modified date:2022.05.06





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Homepage
https://kyushu-u.pure.elsevier.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
  • 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.
Academic Activities
Papers
1. 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, 2022.04.
2. 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.
3. 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<sup>+</sup> 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..
4. 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.
5. 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..
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. Maehara T, Moriyama M, Nakamura S., Pathogenesis of IgG4-related disease: a critical review., Odontology, doi: 10.1007/s10266-018-0377-y., 2018.07.
13. 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].
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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..
20. 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
1. Takashi Maehara, ○ Perugino Cory, Naoki Kaneko, ... , John Stone, Shiv Pillai, Clonally Expanded CD4+ Cytotoxic T Cells, Endothelial Cell Apoptosis and the Pathogenesis of Early Systemic Sclerosis, American College of Rheumatology (2019 ACR/ARP annual meeting), 2019.11.
2. Perugino Cory, Naoki Kaneko, Takashi Maehara, ... , John Stone, Shiv Pillai, CD8+ Cytotoxic T Lymphocytes Are Clonally-expanded in IgG4-related Disease and Home to Affected Tissues, American College of Rheumatology (2019 ACR/ARP annual meeting), 2019.11.
3. Perugino Cory, Naoki Kaneko, Takashi Maehara, Hamid Mattoo, ... John Stone, Shiv Pillai., Clonal Expansion of a Specific Subset of Cytotoxic CD4+T Cells and Tissue Apoptosis in Patients with IgG4-related Disease, American College of Rheumatology (2019 ACR/ARP annual meeting), 2019.11.
4. Takashi Maehara, Seiji Nakamura, A novel disease entity, IgG4-related disease: Immunological insights into the pathogenesis, The 9th Japan-Thailand-Korea Joint Symposium, 2019.11.
5. Takashi Maehara, A Novel diseases discovered and established in 21st Century: IgG4-related disease
- Mechanistic insights from both clinical and immunologic understanding of this condition -, Kyudai Oral Bioscience & OBT Research Center Joint International Symposium 2019, 2019.03.
6. Maehara Takashi, Human BATF+IL-4+ T follicular helper cells are linked to polarized IgG4 switching event and accumulate primarily outside germinal centers in IgG4-related disease , International symposium on IgG4-RD & Fibrosis, 2017.02.
7. Takashi Maehara and Shiv Pillai, Human BATF+ IL-4+ T follicular helper cells are linked to a polarized IgG4 switching event and accumulate primarily IgG4-related disease lesions., Kyushu-University Oral Bio Science, 2017.02.
8. TAKASHI Maehara1, HAMID Mattoo2, NORIKO Ishiguro1, MASAFUMI Moriyama1, SEIJI Nakamura1, SHIV Pillai2. 1. Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science Kyushu University, Fukuoka, Japan 2. Ragon Institute of MGH, MIT, and Harvard, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA, The expansion in lymphoid organs of IL-4+BATF+TFH cells is linked to IgG4 class switching in vivo, IADR, 2018.07.
9. Maehara Takashi, Interleukin-21 contribute to germinal centers formation and IgG4 production in IgG4-related dacryoadenitis and sialoadenitis,so called Mikulicz’s disease., 10th Asian Congress on Oral and Maxillofacial Surgery., 2012.11.
10. Maehara Takashi, Localization of Th subsets in salivary glands of Sjögren’s syndrome., 11th International Symposium on Sjogren's Syndrome., 2011.10.
11. Maehara Takashi, Localization of Th subsets in salivary glands of Sjögren’s syndrome. , The 59th Annual Meeting of Japanese Association for Dental Research., 2011.10.
12. Maehara Takashi, Localization of Th subsets in lesions of Sjögren’s syndrome., International Association for Dental Research., 2011.03.
13. Maehara Takashi, Localization of Th subsets in lesions of Sjögren’s syndrome., International Association for Dental Research., 2010.07.
Membership in Academic Society
  • International Association of Dental Research