Critical Roles of c-Rel in Autoimmune Inflammation and Helper T Cell Differentiation

J Clin Invest. 2002 Sep;110(6):843-50. doi: 10.1172/JCI15254.

Abstract

Different members of the Rel/NF-kappaB family may play different roles in immunity and inflammation. We report here that c-Rel-deficient mice are resistant to autoimmune encephalomyelitis and are defective in Th1, but not Th2 responses. The Th1 deficiency appears to be caused by selective blockade of IL-12 production by c-Rel-deficient antigen-presenting cells, as well as by a complete abrogation of IFN-gamma expression in c-Rel-deficient T cells. Interestingly, c-Rel deficiency does not affect T-bet expression, suggesting that c-Rel may act downstream of T-bet during Th1 cell differentiation. Thus, unlike NF-kappaB1, which selectively regulates Th2 cell differentiation, c-Rel is essential for Th1 cell differentiation and Th1 cell-mediated autoimmune inflammation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Cell Differentiation / physiology*
  • Chimera
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Gene Expression Regulation
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interleukins / immunology
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-rel / genetics
  • Proto-Oncogene Proteins c-rel / immunology*
  • Proto-Oncogene Proteins c-rel / metabolism*
  • Spinal Cord / cytology
  • Spinal Cord / metabolism
  • T-Box Domain Proteins
  • T-Lymphocytes, Helper-Inducer / physiology*
  • Transcription Factors / metabolism

Substances

  • Antibodies, Monoclonal
  • Interleukins
  • NF-kappa B
  • Proto-Oncogene Proteins c-rel
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Interferon-gamma