Toll-like receptor 2 signaling in CD4(+) T lymphocytes promotes T helper 17 responses and regulates the pathogenesis of autoimmune disease

Immunity. 2010 May 28;32(5):692-702. doi: 10.1016/j.immuni.2010.04.010. Epub 2010 Apr 29.

Abstract

Toll-like receptors (TLRs) have previously been shown to play critical roles in the activation of innate immunity. Here, we describe that T cell expression of TLR2 regulates T helper 17 (Th17) cell responses. Stimulation with TLR2 agonists promoted Th17 differentiation in vitro and led to more robust proliferation and Th17 cytokine production. Using the experimental autoimmune encephalomyelitis (EAE) model, we found that TLR2 regulated Th17 cell-mediated autoimmunity in vivo and that loss of TLR2 in CD4(+) T cells dramatically ameliorated EAE. This study thus reveals a critical role of a TLR in the direct regulation of adaptive immune response and pathogenesis of autoimmune diseases.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Deletion
  • Interleukin-17 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Signal Transduction*
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / physiology*

Substances

  • Interleukin-17
  • Toll-Like Receptor 2