Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-β production

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• 作者：Wei Wu ; Hou-Pu Liu ; Feidi Chen ; Han Liu ; Anthony T. Cao ; Suxia Yao ; Mingming Sun ; Heather L. Evans-Marin ; Ye Zhao ; Qing Zhao ; L. Wayne Duck ; Charles O. Elson ; Zhanju Liu and Yingzi Cong
• 关键词：Commensal A4 bacteria ; Dendritic cell ; Th2 ; TGF-&beta
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：46
• 期：5
• 页码：1162-1167
• 全文大小：827K
• ISSN：1521-4141

文摘

It has been shown that while commensal bacteria promote Th1, Th17 and Treg cells in lamina propria (LP) in steady-state conditions, they suppress mucosal Th2 cells. However, it is still unclear whether there are specific commensal organisms down-regulating Th2 responses, and the mechanism involved. Here we demonstrate that commensal A4 bacteria, a member of the Lachnospiraceae family, which produce an immunodominant microbiota CBir1 antigen, inhibits LP Th2-cell development. When transferred into the intestines of RAG^−/− mice, CBir1-specific T cells developed predominately towards Th1 cells and Th17 cells, but to a lesser extent into Th2 cells. The addition of A4 bacterial lysates to CD4⁺ T-cell cultures inhibited production of IL-4. A4 bacteria stimulated dendritic cell production of TGF-β, and blockade of TGF-β abrogated A4 bacteria inhibition of Th2-cell development in vitro and in vivo. Collectively, our data show that A4 bacteria inhibit Th2-cell differentiation by inducing dendritic cell production of TGF-β.