A protective function for interleukin 17A in T cell-mediated intestinal inflammation

Nat Immunol. 2009 Jun;10(6):603-9. doi: 10.1038/ni.1736.

Abstract

Interleukin 23 (IL-23) and IL-17 have been linked to the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease. Yet as an important function for IL-23 is emerging, the function of IL-17 in inflammatory bowel disease remains unclear. Here we demonstrate IL-17A-mediated protection in the CD45RBhi transfer model of colitis. An accelerated wasting disease elicited by T cells deficient in IL-17A correlated with higher expression of genes encoding T helper type 1-type cytokines in colon tissue. IL-17A also modulated T helper type 1 polarization in vitro. Furthermore, T cells deficient in the IL-17 receptor elicited an accelerated, aggressive wasting disease relative to that elicited by wild-type T cells in recipient mice. Our data demonstrate a protective function for IL-17 and identify T cells as not only the source but also a target of IL-17 in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Colitis / immunology*
  • Disease Models, Animal
  • Gene Expression Profiling
  • Interferon-gamma
  • Interleukin-17 / immunology*
  • Interleukin-17 / metabolism
  • Leukocyte Common Antigens / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, Interleukin-17 / immunology
  • T-Box Domain Proteins / metabolism
  • Th1 Cells / immunology*
  • Wasting Syndrome / immunology*

Substances

  • Il17a protein, mouse
  • Il17ra protein, mouse
  • Interleukin-17
  • Receptors, Interleukin-17
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Interferon-gamma
  • Leukocyte Common Antigens