期刊
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
卷 1, 期 3, 页码 295-310出版社
ELSEVIER INC
DOI: 10.1016/j.jcmgh.2015.01.002
关键词
Experimental Colitis; IBD; Immunoregulation; Regulatory B Cells
资金
- Crohn's and Colitis Foundation of America (CCFA)
- Gnotobiotic Animal Facility
- National Institutes of Health [P01 DK094779, R01 DK53347, P40 OD010995, P30DK34987, P30CA016086]
BACKGROUND & AIMS: The regulatory roles of interleukin-10 (IL10)-producing B cells in colitis are not fully understood, so we explored the molecular mechanisms by which these cells modulate mucosal homeostasis. METHODS: CD4(+) T cells from wild-type (WT), Il10(-/-), or Il27ra(-/-) mice were cotransferred with B cells from specific pathogen-free (SPF) or germ-free (GF) WT or Il10(-/-) mice into Rag2(-/-) Il10(-/-)(double-knockout) mice, and the severity of colitis and intestinal regulatory T-cell populations were characterized. In vitro, WT or Il10(-/-) B cells were cocultured with unfractionated, naive or regulatory T cells plus Il10(-/-) antigenpresenting cells and stimulated with cecal bacterial lysate (CBL) with or without IL27 or anti-IL10R blockade. Gene expressions, cytokines in the supernatant and cell populations were assessed. RESULTS: WT but not Il10(-/-) B cells attenuated T helper cell T(H)1/T(H)17-mediated colitis in double-knockout mice that also received WT but not Il10(-/-) T cells. In vitro, CBL-stimulated WT B cells secrete abundant IL10 and suppress interferon-gamma (IFN gamma) and IL17a-production by T cells without requiring cell contact. Although both WT and Il10(-/-) B cells induced Foxp3(+)CD4(+) T-regulatory cells, only WT B cells induced IL10-producing (Foxp3-negative) T regulatory-1 (Tr-1) cells both in vivo and in vitro. However, IL10-producing B cells did not attenuate colitis or induce Tr-1 cells in the absence of T cell IL27 signaling in vivo. WT B cell-dependent Tr-1 induction and concomitant decreased IFN gamma-secretion were also mediated by T-cell IL27-signaling in vitro. CONCLUSIONS: IL10-secreting B cells activated by physiologically relevant bacteria ameliorate T-cell-mediated colitis and contribute to intestinal homeostasis by suppressing effector T cells and inducing Tr-1 cells via IL27-signaling on T cells.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据