Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis

Nat Immunol. 2009 Nov;10(11):1178-84. doi: 10.1038/ni.1791. Epub 2009 Sep 27.

Abstract

Regulatory T cells (T(reg) cells) that express the transcription factor Foxp3 suppress the activity of other cells. Here we show that interleukin 10 (IL-10) produced by CD11b(+) myeloid cells in recombination-activating gene 1-deficient (Rag1(-/-)) recipient mice was needed to prevent the colitis induced by transferred CD4(+)CD45RB(hi) T cells. In Il10(-/-)Rag1(-/-) mice, T(reg) cells failed to maintain Foxp3 expression and regulatory activity. The loss of Foxp3 expression occurred only in recipients with colitis, which indicates that the requirement for IL-10 is manifested in the presence of inflammation. IL-10 receptor-deficient (Il10rb(-/-)) T(reg) cells also failed to maintain Foxp3 expression, which suggested that host IL-10 acted directly on the T(reg) cells. Our data indicate that IL-10 released from myeloid cells acts in a paracrine manner on T(reg) cells to maintain Foxp3 expression.

Publication types

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

MeSH terms

  • Adoptive Transfer
  • Animals
  • CD11 Antigens / immunology
  • Colitis / immunology*
  • Disease Models, Animal
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Intestines / immunology
  • Macrophages / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mucous Membrane / immunology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CD11 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-10