Roles of BCL-3 in the development of TFH cells and the pathogenesis of rheumatoid arthritis
Project/Area Number |
26461460
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Collagenous pathology/Allergology
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Research Institution | Chiba University |
Principal Investigator |
SUZUKI Kotaro 千葉大学, 医学部附属病院, 講師 (90554634)
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Co-Investigator(Kenkyū-buntansha) |
池田 啓 千葉大学, 医学部附属病院, 助教 (10456014)
廣瀬 晃一 千葉大学, 大学院医学研究院, 准教授 (90400887)
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Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 関節リウマチ / Bcl-3 / Bcl-6 / 濾胞ヘルパーT細胞 / BCL-3 / BCL-6 / CD4陽性T細胞 / Tfh細胞 / BCL-3 |
Outline of Final Research Achievements |
We have previously shown that expression of the Bcl-3 gene is down-regulated in CD4+ T cells from patients with rheumatoid arthritis (RA) following tocilizumab therapy. The objective of this study was to examine the role of Bcl-3 in the pathogenesis of RA. We examined the roles of IL-6 signaling in the induction of Bcl-3. We analyzed the gene expression profiles of Bcl-3-transduced CD4+ T cells by RNA sequencing. The effects of enforced expression of Bcl-3 on the development of follicular helper T (Tfh) cells were evaluated. IL-6 induced Bcl-3 expression in CD4+ T cells in a STAT3-dependent manner. Transcriptome analysis revealed that the expression of Bcl-6, a master regulator of Tfh cell differentiation, was significantly up-regulated by the enforced Bcl-3 expression. The enforced Bcl-3 expression increased the numbers of IL-21-producing Tfh-like cells. Bcl-3 is involved in the development of Tfh cells and the pathogenesis of RA, presumably by inducing IL-21 production.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] IkBNS enhances follicular helper T-cell differentiation and function downstream of ASCL2.2016
Author(s)
Hosokawa J, Suzuki K, Meguro K, Tanaka S, Maezawa Y, Suto A, Fujimura L, Sakamoto A, Clevers H, Ohara O, Nakajima H.
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Journal Title
J Allergy Clin Immunol.
Volume: S0091-6749
Issue: 1
Pages: 32476-32479
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] MMP12 is produced by M2 monocytes-macrophages and plays important roles in the development of contact hypersensitivity2015
Author(s)
Nakagomi D, Suzuki K, Meguro K, Hosokawa J, Tamachi T, Takatori H, Suto A, Matsue H, Ohara O, Nakayama T, Shimada S, Nakajima H
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Journal Title
J Allergy Clin Immunol
Volume: 135
Issue: 5
Pages: 1397-400
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Roles of B Cell Leukemia/Lymphoma 3 in the development of T follicular helper cells and the pathogenesis of rheumatoid arthritis.2015
Author(s)
Meguro, K., Suzuki, K., Hosokawa, J., Sanayama, Y., Tanaka, S., Furuta, S., Ikeda, K., Takatori, H, Suto, A., Sakamoto, A., Ohara, O., Nakajima, H.
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Journal Title
Arthritis & Rheumatology
Volume: 67
Issue: 10
Pages: 2651-60
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Ezh2 loss promotes development of myelodysplastic syndrome but attenuates its predisposition to leukemic transformation.2014
Author(s)
Sashida, G., Harada, H., Matsui, H., Oshima, M., Yui, M., Harada, Y., Tanaka, S., Mochizuki-Kashio, M., Wang, C., Saraya, A., Muto, T., Hayasi, Y., Suzuki, K., Nakajima, H., Inaba, T., Koseki, H., Huang, G., Kitamura, T. and Iwama, A.
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Journal Title
Nat. Commun.
Volume: 5
Issue: 1
Pages: 5177-5177
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Sox5 and c-Maf cooperatively induce Th17 cell differentiation via ROR gamma t induction as downstream targets of Stat32014
Author(s)
Tanaka S, Suto A, Iwamoto T, Kashiwakuma D, Kagami S, Suzuki K, Takatori H, Tamachi T, Hirose K, Onodera A, Suzuki J, Ohara O, Yamashita M, Nakayama T, Nakajima H
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Journal Title
J Exp Med
Volume: 211
Issue: 9
Pages: 1857-1874
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Roles of B Cell Leukemia/Lymphoma 3 in the Development of T Follicular Helper Cells and the Pathogenesis of Rheumatoid Arthritis.2015
Author(s)
K. Meguro, K. Suzuki, J. Hosokawa, Y. Sanayama, S. Tanaka, S. Furuta, K. Ikeda, H. Takatori, A. Suto, O. Ohara, H. Nakajima
Organizer
Annual Congress of the European League against Rheumatism
Place of Presentation
ローマ イタリア
Year and Date
2015-06-10
Related Report
Int'l Joint Research
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[Presentation] Sox5 and c-mad cooperatively induce Th17 cell differentiation via RORgt induction as downstream targets of Stat3.2014
Author(s)
Tanaka S, Suto A, Iwamoto T, Suzuki K, Takatori H, Tamachi T, Hirose K, Onodera A, Suzuki J, Ohara O, Yamashita M, Nakayama T, Nakajima H.
Organizer
第43回日本免疫学会総会•学術集会
Place of Presentation
国立京都国際会館 (京都府京都市)
Year and Date
2014-12-12
Related Report