2021 Fiscal Year Final Research Report
Antifibrotic effect of regulating Th17 and regulatory T cell imbalance and intestinal microbiota changes in a systemic sclerosis mouse model
| Project/Area Number |
20K17308
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53050:Dermatology-related
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2022-03-31
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| Keywords | 全身性強皮症 / Th17細胞・制御性T細胞バランス / 寄生虫感染症 / 蠕虫 / 皮膚線維化 |
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| Outline of Final Research Achievements |
To elucidate the involvement of Th17/regulatory T (Treg) cell balance in the pathogenesis of systemic sclerosis (SSc), we investigated the effect of intestinal parasite (Heligmosomoides polygyrus (Hp)) infection-induced Treg cells activation on the bleomycin-induced SSc mouse model. As a result, Hp infection increases Treg cells and suppresses bleomycin-induced Th17 cells, leading to an inhibitory effect on fibrosis. Furthermore, analysis of the intestinal microbiota of mice and SSc patients revealed that alterations of intestinal microbiota could be involved in the Th17/Treg cell imbalance in SSc and in the development and progression of the disease. In conclusion, Th17/Treg imbalance may be involved in the pathogenesis of SSc, and proper regulation of Th17/Treg balance may be a new therapeutic target.
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| Free Research Field |
皮膚科学
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| Academic Significance and Societal Importance of the Research Achievements |
全身性強皮症は、免疫異常を基盤として、皮膚および内臓臓器の線維化、血管異常を呈する全身性疾患である。本邦の患者数は約2万人であり、難病指定されている。本研究成果によって、強皮症の皮膚線維化の病態における制御性T細胞とTh17細胞のバランス異常の解明につながり、制御性T細胞の活性化が強皮症の皮膚線維化を改善させる新たな治療法につながる可能性が期待される。強皮症の病態と腸内細菌叢との関連も新たな知見が得られることが予想される。制御性T細胞の誘導に関わる細菌叢と線維化の病態への関与が解明されれば、強皮症患者が特定の腸内細菌を摂取することで線維化の治療につながる可能性も期待される。
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