1. Critical regulation of CD4+ T cell survival and autoimmunity by β-arrestin 1
- Author
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Dangsheng Li, Ju Qiu, Gang Pei, Jingwu Z Zhang, Zhenxin Li, Zhengliang Guo, Chuanzhen Lu, Enguang Bi, Lei Zang, Yan Feng, Yufeng Shi, Wei Cao, Chang Liu, and Jiuhong Kang
- Subjects
CD4-Positive T-Lymphocytes ,Cell signaling ,Encephalomyelitis, Autoimmune, Experimental ,Multiple Sclerosis ,Arrestins ,Cell Survival ,medicine.medical_treatment ,T cell ,Immunoblotting ,Immunology ,Apoptosis ,Autoimmunity ,Biology ,medicine.disease_cause ,Proto-Oncogene Mas ,Epigenesis, Genetic ,Mice ,Immune system ,medicine ,Animals ,Humans ,Immunology and Allergy ,beta-Arrestins ,Reverse Transcriptase Polymerase Chain Reaction ,Experimental autoimmune encephalomyelitis ,Flow Cytometry ,medicine.disease ,Acquired immune system ,beta-Arrestin 1 ,Cytokine ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,Cancer research ,Arrestin beta 2 - 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.
- Published
- 2007
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