title: Critical regulation of CD4+ T cell survival and autoimmunity by beta-arrestin 1.
abstract: CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein beta-arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through beta-arrestin 1-dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding beta-arrestin 1 (Arrb1) were much more resistant to experimental autoimmune encephalomyelitis, whereas overexpression of Arrb1 increased susceptibility to this disease. CD4+ T cells from patients with multiple sclerosis had much higher Arrb1 expression, and 'knockdown' of Arrb1 by RNA-mediated interference in those cells increased apoptosis induced by cytokine withdrawal. Our data demonstrate that beta-arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.
authors.affiliation: Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate School of the Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Shi
authors.forename: Yan
authors.initials: Y
authors.lastname: Feng
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Zhenxin
authors.initials: Z
authors.lastname: Li
authors.forename: Dangsheng
authors.initials: D
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Ju
authors.initials: J
authors.lastname: Qiu
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Guo
authors.forename: Enguang
authors.initials: E
authors.lastname: Bi
authors.forename: Lei
authors.initials: L
authors.lastname: Zang
authors.forename: Chuanzhen
authors.initials: C
authors.lastname: Lu
authors.forename: Jingwu Z
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D019390:Arrestins / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002470:Cell Survival / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D051379:Mice; D009103:Multiple Sclerosis / Q000276:immunology / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
chemical_list: C000605253:ARRB1 protein, human; C000605255:Arrb1 protein, mouse; D019390:Arrestins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins