Memory/effector (CD45RB(lo)) CD4 T cells are controlled directly by IL-10 and cause IL-22-dependent intestinal pathology

J Exp Med. 2011 May 9;208(5):1027-40. doi: 10.1084/jem.20102149. Epub 2011 Apr 25.

Abstract

The role of direct IL-10 signaling in different T cell subsets is not well understood. To address this, we generated transgenic mice expressing a dominant-negative IL-10 receptor specifically in T cells (CD4dnIL-10Rα). We found that Foxp3-depleted CD45RB(lo) (regulatory T cell [T(reg) cell]-depleted CD45RB(lo)) but not CD45RB(hi) CD4(+) T cells are controlled directly by IL-10 upon transfer into Rag1 knockout (KO) mice. Furthermore, the colitis induced by transfer of T(reg) cell-depleted CD45RB(lo) CD4(+) T cells into Rag1 KO mice was characterized by reduced Th1 and increased Th17 cytokine messenger RNA levels in the colon as compared with the colitis induced by transfer of CD45RB(hi) T cells. In contrast to the CD45RB(hi) transfer colitis model, in which IL-22 is protective, we found that T cell-derived IL-22 was pathogenic upon transfer of T(reg) cell-depleted CD45RB(lo) T cells into Rag1 KO mice. Our results highlight characteristic differences between colitis induced by naive (CD45RB(hi)) and memory/effector (T(reg) cell-depleted CD45RB(lo)) cells and different ways that IL-22 impacts inflammatory bowel disease.

Publication types

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

MeSH terms

  • Animals
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / metabolism
  • Colitis / pathology
  • Colon / immunology
  • Colon / metabolism
  • Colon / pathology
  • Homeodomain Proteins / immunology
  • Homeodomain Proteins / metabolism
  • Humans
  • Immunologic Memory*
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology*
  • Interleukin-10 / metabolism
  • Interleukin-22
  • Interleukins / genetics
  • Interleukins / immunology*
  • Interleukins / metabolism
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / immunology*
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Mice, Knockout
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism
  • Th17 Cells / pathology

Substances

  • Homeodomain Proteins
  • IL10 protein, human
  • IL10 protein, mouse
  • Interleukins
  • RAG-1 protein
  • Interleukin-10
  • Leukocyte Common Antigens