Microbiota maintain colonic homeostasis by activating TLR2/MyD88/PI3K signaling in IL-10-producing regulatory B cells.
- Resource Type
- journal article
- Authors
- Yoshiyuki Mishima; Akihiko Oka; Bo Liu; Herzog, Jeremy W.; Chang Soo Eun; Ting-Jia Fan; Bulik-Sullivan, Emily; Carroll, Ian M.; Hansen, Jonathan J.; Liang Chen; Wilson, Justin E.; Fisher, Nancy C.; Ting, Jenny P. Y.; Tomonori Nochi; Wahl, Angela; Garcia, J. Victor; Karp, Christopher L.; Sartor, R. Balfour; Mishima, Yoshiyuki; Oka, Akihiko
- Source
- Journal of Clinical Investigation. Sep2019, Vol. 129 Issue 9, p3702-3716. 15p.
- Subject
- *B cells
*HOMEOSTASIS
*T cells
*ENTEROBACTERIACEAE
*FECAL microbiota transplantation
*PROTEIN metabolism
*INTERLEUKINS
*BIOCHEMISTRY
*CYTOKINES
*RESEARCH
*PHOSPHOTRANSFERASES
*PHENOMENOLOGICAL biology
*ANIMAL experimentation
*MICROBIOLOGY
*INFLAMMATION
*RESEARCH methodology
*REGULATORY B cells
*CELL receptors
*EVALUATION research
*COMPARATIVE studies
*IMMUNITY
*RESEARCH funding
*COLITIS
*CARRIER proteins
*MICE
*INTESTINES
- Language
- ISSN
- 0021-9738
Resident microbiota activate regulatory cells that modulate intestinal inflammation and promote and maintain intestinal homeostasis. IL-10 is a key mediator of immune regulatory function. Our studies described the functional importance and mechanisms by which gut microbiota and specific microbial components influenced the development of intestinal IL-10-producing B cells. We used fecal transplant to germ-free (GF) Il10+/EGFP reporter and Il10-/- mice to demonstrate 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 down-regulated microbiota-activated mucosal inflammatory cytokines. TLR2/9 ligands and enteric bacterial lysates preferentially induced IL-10 production and regulatory capacity of intestinal B cells. Analysis of Il10+/EGFP mice crossed with additional gene-deficient strains and B cell co-transfer 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 PI3Kp110δ and AKT downstream signaling. 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. [ABSTRACT FROM AUTHOR]