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