Critical regulation of CD4+ T cell survival and autoimmunity by beta-arrestin 1.
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.
Shi
Yufeng
Y
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.
Feng
Yan
Y
Kang
Jiuhong
J
Liu
Chang
C
Li
Zhenxin
Z
Li
Dangsheng
D
Cao
Wei
W
Qiu
Ju
J
Guo
Zhengliang
Z
Bi
Enguang
E
Zang
Lei
L
Lu
Chuanzhen
C
Zhang
Jingwu Z
JZ
Pei
Gang
G
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
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