2020 Fiscal Year Final Research Report
Microbiota-derived butyrate limits the autoimmune response by promoting the differentiation of follicular regulatory T cells
| Project/Area Number |
17K15734
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Immunology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | 酪酸 / 濾胞制御性T細胞数 / 間接リウマチ |
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| Outline of Final Research Achievements |
We found that butyrate, one of the short-chain fatty acids produced by the gut commensal bacteria, significantly decreased in the intestinal tract of the early stages untreated rheumatoid arthritis patients compared to healthy people. Furthermore, we found that the treatment of the butyrate diet mitigated the development of an autoimmune rheumatoid arthritis model in mice. Butyrate increased the number of follicular regulatory T cells and suppressed the production of autoantibodies required for the development of arthritis. Moreover, we developed a new follicular regulatory T cell culture system and examined the mechanism of induction of follicular regulatory T cell differentiation by butyrate. Using the culture system, we found that butyrate promotes the differentiation of follicular regulatory T cells by inducing the expression of the transcriptional repressor Bcl-6, which is essential for the differentiation through its histone deacetylase inhibitory action.
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| Free Research Field |
免疫学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、発症初期の未治療の関節リウマチ患者の腸管内の酪酸濃度が健常者と比較して顕著に低い事を明らかにしている。さらに、酪酸産生菌が顕著に減少することを見出した。これは、腸内の酪酸産生が減少することと関節リウマチの発症との関連性を示す成果である。実際マウス関節リウマチモデルを用いた検討から、酪酸産生菌により酪酸が産生される飼料を与えることで、関節炎の症状が著明に改善した。以上のことから、発症初期の関節リウマチ患者へ酪酸が産生される食事を予防的に提供することで、将来的な症状を抑制できると考えている。これを既存薬と合わせて使用し、効果的な関節リウマチ治療法に結び付くと期待している。
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