Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation.
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.
Hilliard
Brendan A
BA
Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Mason
Nicola
N
Xu
Lingyun
L
Sun
Jing
J
Lamhamedi-Cherradi
Salah-Eddine
SE
Liou
Hsiou-Chi
HC
Hunter
Christopher
C
Chen
Youhai H
YH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002678:Chimera; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism; D020825:T-Box Domain Proteins; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D000098815:T-bet Transcription Factor
D000911:Antibodies, Monoclonal; D007378:Interleukins; D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors; D007371:Interferon-gamma