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- Title
Critical regulation of CD4<sup>+</sup> T cell survival and autoimmunity by β-arrestin 1.
- Authors
Shi, Yufeng; Feng, Yan; Kang, Jiuhong; Liu, Chang; Li, Zhenxin; Li, Dangsheng; Cao, Wei; Qiu, Ju; Guo, Zhengliang; Bi, Enguang; Zang, Lei; Lu, Chuanzhen; Zhang, Jingwu Z; Pei, Gang
- Abstract
CD4+ T cells are important in adaptive immunity, but their dysregulation can cause autoimmunity. Here we demonstrate that the multifunctional adaptor protein β-arrestin 1 positively regulated naive and activated CD4+ T cell survival. We found enhanced expression of the proto-oncogene Bcl2 through β-arrestin 1–dependent regulation of acetylation of histone H4 at the Bcl2 promoter. Mice deficient in the gene encoding β-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 β-arrestin 1 is critical for CD4+ T cell survival and is a factor in susceptibility to autoimmunity.
- Publication
Nature Immunology, 2007, Vol 8, Issue 8, p817
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni1489