Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells
- Title
- Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells
- Author
- 은창수
- Keywords
- INFLAMMATORY-BOWEL-DISEASE; T-CELLS; ULCERATIVE-COLITIS; INTESTINAL MICROBIOTA; IMMUNE-RESPONSES; MEDIATED COLITIS; INTERLEUKIN-10; BACTERIA; IL-10; COMMENSAL
- Issue Date
- 2019-09
- Publisher
- AMER SOC CLINICAL INVESTIGATION INC
- Citation
- JOURNAL OF CLINICAL INVESTIGATION, v. 129, no. 9, Page. 3702-3716
- Abstract
- Resident microbiota activates regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies describe the functional importance and mechanisms by which gut microbiota and specific microbial components influence the development of intestinal IL-10-producing B cells. Using fecal transplant into germ-free (GF) Il10(+/EGFP) reporter and Il10(-/-) mice, we demonstrated that microbiota from specific pathogen-free mice primarily stimulated IL-10-producing colon-specific B cells and T regulatory 1 cells in ex-GF mice. IL-10 in turn downregulated microbiota-activated mucosal inflammatory cytokines. TLR2 and -9 ligands and enteric bacterial lysates preferentially induced IL-10 production and the regulatory capacity of intestinal B cells. Analysis of Il10(+/EGFP) mice crossed with additional gene-deficient strains and B cell cotransfer studies demonstrated that microbiota-induced IL-10-producing intestinal B cells ameliorated chronic T cell-mediated colitis in a TLR2-, MyD88-, and PI3K-dependent fashion. In vitro studies implicated downstream signaling of PI3Kp110 delta and AKT. These studies demonstrated that resident enteric bacteria activated intestinal IL-10-producing B cells through TLR2, MyD88, and PI3K pathways. These B cells reduced colonic T cell activation and maintained mucosal homeostasis in response to intestinal microbiota.
- URI
- https://www.jci.org/articles/view/93820https://repository.hanyang.ac.kr/handle/20.500.11754/153731
- ISSN
- 0021-9738; 1558-8238
- DOI
- 10.1172/JCI93820
- Appears in Collections:
- COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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