| Project/Area Number |
17K09969
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Collagenous pathology/Allergology
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| Research Institution | Chiba University |
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Principal Investigator |
SUZUKI KOTARO 千葉大学, 大学院医学研究院, 准教授 (90554634)
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| Co-Investigator(Kenkyū-buntansha) |
中島 裕史 千葉大学, 大学院医学研究院, 教授 (00322024)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 濾胞ヘルパーT細胞 / SLE / CD4陽性T細胞 / Ascl2 / ASCL2 |
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| Outline of Final Research Achievements |
It has been well known that follicular helper T cells (Tfh cells), a subset of CD4 T cells, are involved in the pathogenesis of systemic lupus erythematosus (SLE). In addition, achaete-scute homologue 2 (Ascl2), a basic-helix-loop-helix family member protein, plays an important role in Tfh cell development. However, roles of Ascl2 in Tfh cell development in SLE has been undetermined. In this study, I examined Tfh cell development in a imiquimod-induced lupus model using CD4-specific Ascl2-deficient mice. The number of Tfh cells was decreased in CD4-specific Ascl2-deficient mice as compared with that in control mice. Moreover, expression of CXCR5 and PD-1 on Tfh cells were decreased in CD4-specific Ascl2-deficient mice as compared with that in control mice. These results suggest that Ascl2 plays an important role in Tfh cell development in SLE.
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| Academic Significance and Societal Importance of the Research Achievements |
濾胞ヘルパーT細胞(Tfh細胞）は、リンパ節胚中心においてB細胞が抗原高親和性の抗体を産生するのに必須なCD4陽性T細胞のサブタイプであり、全身性エリテマトーデス(SLE)などの自己免疫疾患の発症にも関与していることが報告されている。近年、ヘリックスループヘリックスファミリーであるAscl2がTfh細胞分化に重要であることが示されたが、自己免疫疾患の発症時におけるTfh細胞の分化にAscl2が重要であるか否かについては不明だった。今回の研究でAscl2がSLE発症時のTfh細胞分化に重要な役割を果たしていることが明らかになり、Ascl2が SLEの治療ターゲットになりうる可能性が示唆された。
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