Commensal A4 bacteria inhibit intestinal Th2‐cell responses through induction of dendritic cell TGF‐β production |
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Authors: | 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 Yingzi Cong |
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Affiliation: | 1. Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA;2. Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China;3. Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA;4. Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China;5. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA |
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Abstract: | 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. |
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Keywords: | Commensal A4 bacteria Dendritic cell Th2 TGF‐β |
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