Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice
Microbiotas from Humans with Inflammatory Bowel Disease Alter the Balance of Gut Th17 and RORγt+ Regulatory T Cells and Exacerbate Colitis in Mice
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DOI：
10.1016/j.immuni.2018.12.015
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发表时间：
2019-01-15
期刊：
影响因子：
32.4
通讯作者：
Faith, Jeremiah J.
中科院分区：
文献类型：
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作者：
Britton, Graham J.;Contijoch, Eduardo J.;Faith, Jeremiah J.
微生物区系被认为影响炎症性肠病(IBD)的发生和发展，但确定微生物区系对IBD病因学的普遍影响需要更大规模的功能分析。我们用来自30名健康和IBD捐赠者的肠道微生物定植了无菌小鼠，并测定了肠道T细胞对每个微生物群的动态平衡反应。与来自健康捐赠者的微生物相比，将IBD微生物转移到无菌小鼠中增加了肠道Th17细胞和Th2细胞的数量，减少了ROR Gamma t(+)Treg细胞的数量。IBD微生物的定植加剧了结肠炎模型中的疾病，在该模型中，将原始T细胞转移到Rag1(-/-)小鼠中会导致结肠炎。在Rag1(-/-)结肠炎模型中，每个微生物群诱导的Th17和ROR-Gamma t(+)Treg细胞的比例可以预测人类的疾病状态，并解释了疾病的严重程度。因此，对肠道Th17和ROR-Gamma t(+)Treg细胞室的影响成为IBD微生物群的一个统一特征，表明微生物在IBD发病机制中的作用。
Microbiota are thought to influence the development and progression of inflammatory bowel disease (IBD), but determining generalizable effects of microbiota on IBD etiology requires larger-scale functional analyses. We colonized germ-free mice with intestinal microbiotas from 30 healthy and IBD donors and determined the homeostatic intestinal T cell response to each microbiota. Compared to microbiotas from healthy donors, transfer of IBD microbiotas into germ-free mice increased numbers of intestinal Th17 cells and Th2 cells and decreased numbers of ROR gamma t(+) Treg cells. Colonization with IBD microbiotas exacerbated disease in a model where colitis is induced upon transfer of naive T cells into Rag1(-/-) mice. The proportions of Th17 and ROR gamma t(+) Treg cells induced by each microbiota were predictive of human disease status and accounted for disease severity in the Rag1(-/-) colitis model. Thus, an impact on intestinal Th17 and ROR gamma t(+) Treg cell compartments emerges as a unifying feature of IBD microbiotas, suggesting a general mechanism for microbial contribution to IBD pathogenesis.