Resident bacteria-stimulated IL-10-secreting B cells ameliorate T cell-mediated colitis by inducing Tr-1 cells that require IL-27-signaling.

Background & Aims: Regulatory roles of IL-10-producing B cells in colitis are not fully understood. The aim of this study is to explore the molecular mechanisms by which these cells modulate mucosal homeostasis.

Methods: CD4 T cells from WT, mice were co-transferred with B cells from specific pathogen-free (SPF) or germ-free (GF) WT or mice into (DKO) mice and the severity of colitis and intestinal regulatory T cell populations were characterized. , WT or B cells were co-cultured with unfractionated, naïve or regulatory T cells plus antigen-presenting cells and stimulated with cecal bacterial lysate (CBL) with or without IL-27 or anti-IL-10R blockade. Gene expressions, cytokines in the supernatant and cell populations were assessed.

Results: WT but not B cells attenuate Th1/Th17-mediated colitis in DKO mice that also received WT but not T cells. , CBL-stimulated WT B cells secrete abundant IL-10 and suppress IFNγ and IL-17a-production by T cells without requiring cell contact. Although both WT and B cells induce Foxp3CD4 Tregs, only WT B cells induce IL-10-producing (Foxp3-negative) T regulatory-1 (Tr-1) cells both and . However, IL-10-producing B cells did not attenuate colitis or induce Tr-1 cells in the absence of T cell IL-27-signaling . WT B cell-dependent Tr-1 induction and concomitant decreased IFNγ-secretion were also mediated by T-cell IL-27-signaling .

Conclusions: IL-10-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 IL-27-signaling on T cells.