title: Resident bacteria-stimulated IL-10-secreting B cells ameliorate T cell-mediated colitis by inducing Tr-1 cells that require IL-27-signaling.
abstract: OBJECTIVE
  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,Il10-/-or Il27ra-/-mice were co-transferred with B cells from specific pathogen-free (SPF) or germ-free (GF) WT orIl10-/-mice intoRag2-/-Il10-/-(DKO) mice and the severity of colitis and intestinal regulatory T cell populations were characterized.In vitro, WT orIl10-/-B cells were co-cultured with unfractionated, naïve or regulatory T cells plusIl10-/-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 notIl10-/-B cells attenuate Th1/Th17-mediated colitis in DKO mice that also received WT but notIl10-/-T cells.In vitro, 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 andIl10-/-B cells induce Foxp3+CD4+Tregs, only WT B cells induce IL-10-producing (Foxp3-negative) T regulatory-1 (Tr-1) cells bothin vivoandin vitro. However, IL-10-producing B cells did not attenuate colitis or induce Tr-1 cells in the absence of T cell IL-27-signalingin vivo. WT B cell-dependent Tr-1 induction and concomitant decreased IFNγ-secretion were also mediated by T-cell IL-27-signalingin vitro.
  
  
  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.
authors.affiliation: Center for Gastrointestinal Biology and Disease, Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Mishima
authors.affiliation: Center for Gastrointestinal Biology and Disease, Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill ; Institute of Zoonesis, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.affiliation: Center for Gastrointestinal Biology and Disease, Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Hansen
authors.affiliation: Center for Gastrointestinal Biology and Disease, Department of Medicine, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill ; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.
authors.forename: R Balfour
authors.initials: RB
authors.lastname: Sartor
keywords: IBD; experimental colitis; immunoregulation; regulatory B cells