title: Critical roles of c-Rel in autoimmune inflammation and helper T cell differentiation.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Brendan A
authors.initials: BA
authors.lastname: Hilliard
authors.forename: Nicola
authors.initials: N
authors.lastname: Mason
authors.forename: Lingyun
authors.initials: L
authors.lastname: Xu
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Salah-Eddine
authors.initials: SE
authors.lastname: Lamhamedi-Cherradi
authors.forename: Hsiou-Chi
authors.initials: HC
authors.lastname: Liou
authors.forename: Christopher
authors.initials: C
authors.lastname: Hunter
authors.forename: Youhai H
authors.initials: YH
authors.lastname: Chen
mesh_terms: 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
chemical_list: 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