Probiotic Bifidobacterium breve Induces IL-10-Producing Tr1 Cells in the Colon

PLoS Pathogens

Hiroki Yoshida¹  Masahiro Yamamoto²  Yoshiyasu Ueda²  Ji Su Ma²  Hirokazu Tsuji²  Koji Nomoto³  Kiyoshi Takeda⁴  Takuya Takahashi⁴  Seong Gyu Jeon⁴  Noriko M. Tsuji⁴  Hisako Kayama⁵  Hiroshi Kiyono⁵  Takashi Asahara⁵  Takashi Kusu⁶  Ryu Okumura⁶  Hiromitsu Hara⁶ 

[1] Age Dimension Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan;Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan;Division of Mucosal Immunology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan;Laboratory of Immune Regulation, Department of Microbiology and Immunology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan;WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan;Yakult Central Institute for Microbiological Research, Kunitachi, Tokyo, Japan

关键词: T cells;    Gastrointestinal tract;    Colon;    Probiotics;    Regulatory T cells;    Toll-like receptors;    Microbiome;    Large intestine;   

DOI  :  10.1371/journal.ppat.1002714

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Specific intestinal microbiota has been shown to induce Foxp3+ regulatory T cell development. However, it remains unclear how development of another regulatory T cell subset, Tr1 cells, is regulated in the intestine. Here, we analyzed the role of two probiotic strains of intestinal bacteria, Lactobacillus casei and Bifidobacterium breve in T cell development in the intestine. B. breve, but not L. casei, induced development of IL-10-producing Tr1 cells that express cMaf, IL-21, and Ahr in the large intestine. Intestinal CD103+ dendritic cells (DCs) mediated B. breve-induced development of IL-10-producing T cells. CD103+ DCs from Il10−/−, Tlr2−/−, and Myd88−/− mice showed defective B. breve-induced Tr1 cell development. B. breve-treated CD103+ DCs failed to induce IL-10 production from co-cultured Il27ra−/− T cells. B. breve treatment of Tlr2−/− mice did not increase IL-10-producing T cells in the colonic lamina propria. Thus, B. breve activates intestinal CD103+ DCs to produce IL-10 and IL-27 via the TLR2/MyD88 pathway thereby inducing IL-10-producing Tr1 cells in the large intestine. Oral B. breve administration ameliorated colitis in immunocompromised mice given naïve CD4+ T cells from wild-type mice, but not Il10−/− mice. These findings demonstrate that B. breve prevents intestinal inflammation through the induction of intestinal IL-10-producing Tr1 cells.

【 授权许可】

CC BY