Abstract

CD4⁺ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein -arrestin 1 positively regulated naive and activated CD4⁺ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through -arrestin 1–dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding -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 -arrestin 1 is critical for CD4⁺ T cell survival and is a factor in susceptibility to autoimmunity.

1. 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.
2. Joint Immunology Laboratory of Institute of Health Sciences and Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine and Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
3. Institute of Neurology, Huashan Hospital, Shanghai Medical College of Fudan University, Shanghai 200040, China.
4. Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
5. Department of Neurology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200025, China.
6. E-Institutes of Shanghai Universities, Shanghai 200240, China.

Correspondence to: Gang Pei¹ e-mail: gpei@sibs.ac.cn

Correspondence to: Jingwu Z Zhang^2,5,6 e-mail: jwzang@sibs.ac.cn

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