IL-10-producing regulatory B10 cells inhibit intestinal injury in a mouse model

Am J Pathol. 2011 Feb;178(2):735-43. doi: 10.1016/j.ajpath.2010.10.022.

Abstract

B cells mediate multiple functions that influence immune and inflammatory responses. In mice, the addition of dextran sulfate sodium (DSS) to drinking water leads to immediate intestinal injury. Dextran sulfate sodium-induced intestinal injury serves as an experimental animal model for human ulcerative colitis. The contribution of B cells to DSS-induced intestinal injury is unclear. In this study, we show that DSS-induced intestinal injury was more severe in CD19-deficient (CD19(-/-)) mice than in wild-type mice. These inflammatory responses were negatively regulated by a unique IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells) that was absent in CD19(-/-) mice and represented only 1% to 2% of splenic B220(+) cells in wild-type mice. Remarkably, adoptive transfer of these B10 cells from wild-type mice reduced inflammation in CD19(-/-) mice in an IL-10-dependent manner. These results demonstrate that IL-10 production from regulatory B10 cells regulates DSS-induced intestinal injury. These findings may provide new insights and therapeutic approaches for treating ulcerative colitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD19 / metabolism
  • Antigens, CD1d / metabolism
  • B-Lymphocyte Subsets / immunology*
  • CD5 Antigens / metabolism
  • Colitis / immunology
  • Colitis / pathology
  • Dextran Sulfate
  • Disease Models, Animal
  • Humans
  • Interleukin-10 / biosynthesis*
  • Intestines / immunology*
  • Intestines / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Spleen / immunology

Substances

  • Antigens, CD19
  • Antigens, CD1d
  • CD5 Antigens
  • Interleukin-10
  • Dextran Sulfate