title: Commensal A4 bacteria inhibit intestinal Th2-cell responses through induction of dendritic cell TGF-β production.
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.
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Wei
authors: W
authors: Wu
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Hou-Pu
authors: HP
authors: Liu
authors: Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Feidi
authors: F
authors: Chen
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Gastroenterology, The Qilu Hospital, Shandong University, Shandong, China.
authors: Han
authors: H
authors: Liu
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Anthony T
authors: AT
authors: Cao
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Suxia
authors: S
authors: Yao
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Mingming
authors: M
authors: Sun
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Heather L
authors: HL
authors: Evans-Marin
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Ye
authors: Y
authors: Zhao
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Qing
authors: Q
authors: Zhao
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: L Wayne
authors: LW
authors: Duck
authors: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.
authors: Charles O
authors: CO
authors: Elson
authors: Department of Gastroenterology, The Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
authors: Zhanju
authors: Z
authors: Liu
authors: Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.|Department of Pathology, University of Texas Medical Branch, Galveston, TX, USA.
authors: Yingzi
authors: Y
authors: Cong
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D006094:Gram-Positive Bacteria / Q000737:chemistry / Q000276:immunology*; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology; D013559:Symbiosis; D018417:Th1 Cells / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D015847:Interleukin-4
keywords: Commensal A4 bacteria; Dendritic cell; TGF-β; Th2