| Project/Area Number |
18K08409
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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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| Review Section |
Basic Section 54020:Connective tissue disease and allergy-related
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| Research Institution | Ehime University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | Bach2 / IL-7 / 抗原非依存性Th2免疫応答 / Tpath2 / 脂質代謝 / IL-7 receptor / Th2 / アレルギー性気道炎症 |
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| Outline of Final Research Achievements |
IL-7 and IL-33-dependent (antigen-independent) production of IL-5 and IL-13 from the IL-33 receptor Th2 (IL-33R+ Th2) cells play an important role in the pathogenesis of chronic type 2 airway inflammation. We previously reported that T cell-specific Bach2-deficient mice had a lot of IL-33R+ CD4 T cells in the lung, and spontaneously developed type 2 lung inflammation. Here, we investigate the role of Bach2 in antigen-independent Th2 responses.
We found that the expression of IL-33R in Th2 cells was induced in an IL-7-dependent manner, and Bach2 inhibited IL-7-dependent induction of IL-33R. Furthermore, Bach2 inhibited IL-7R expression and IL-7-signaling in Th2 cells. From these results, we concluded that Bach2 controls antigen-independent Th2 response by regulating the IL-7R expression.
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| Academic Significance and Societal Importance of the Research Achievements |
Bach2はT細胞のアイデンティティを維持するガーディアン転写因子であるという考えが提唱されている。抗原特異性はT細胞アイデンティティの一つである。今回、Bach2の発現低下や欠損がTh2細胞の抗原非依存的免疫応答の亢進や、気道炎症の慢性化につながる可能性が明らかになってきた。T細胞におけるBach2の適切な発現は、肺恒常性の維持に必要であり、その異常はT細胞アイデンティティの破綻を引き起こし、呼吸器疾患の発症につながることが予想される。今後、肺T細胞におけるBach2の詳細な役割解析が、喘息や難治性肺疾患の新規治療法の開発につながることが期待される。
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