Critical regulation of cd4+ t cell survival and autoimmunity by β-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 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.

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REGULATORY T CELLS IN HEALTH AND AUTOIMMUNITY Article Open access 30 July 2024 REGULATION OF CD8+ T MEMORY AND EXHAUSTION BY THE MTOR SIGNALS Article Open access 15 August 2023 REFERENCES *

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references ACKNOWLEDGEMENTS We thank R.J. Lefkowitz (Duke University Medical Center) for rabbit polyclonal anti-β-arrestin (A1CT) and for _Arrb1__−/−_ and _Arrb2__−/−_ mice; Y. Shi, J. Cai

and X. Liu for discussions; and S. Xin, Y. Li, G. Ding, P. Wu and S. Chen for technical assistance. Supported by the Ministry of Science and Technology (2003CB515405 and 2005CB522406), the

National Natural Science Foundation of China (30021003, 30623003, 30625014, 30400230, 30430650 and 30571731), the Shanghai Municipal Commission for Science and Technology (06ZR14098,

04JC14040, 04DZ14902 and PJ200500330), the Shanghai Municipal Health Bureau (LJ06046), the Shanghai Leading Academic Discipline Project (T206) and the Chinese Academy of Sciences

(KSCX2-YW-R-56). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 Yufeng Shi, Jiuhong Kang, Chang Liu, Enguang Bi, Lei Zang & Gang Pei * 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 Yan Feng, Wei Cao, Ju Qiu & Jingwu Z Zhang * Institute of Neurology, Huashan Hospital, Shanghai Medical College of Fudan University,

Shanghai, 200040, China Zhenxin Li & Chuanzhen Lu * Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China Dangsheng Li * Department of

Neurology, Ruijin Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200025, China Zhengliang Guo & Jingwu Z Zhang * E-Institutes of Shanghai Universities, Shanghai,

200240, China Jingwu Z Zhang Authors * Yufeng Shi View author publications You can also search for this author inPubMed Google Scholar * Yan Feng View author publications You can also search

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can also search for this author inPubMed Google Scholar * Wei Cao View author publications You can also search for this author inPubMed Google Scholar * Ju Qiu View author publications You

can also search for this author inPubMed Google Scholar * Zhengliang Guo View author publications You can also search for this author inPubMed Google Scholar * Enguang Bi View author

publications You can also search for this author inPubMed Google Scholar * Lei Zang View author publications You can also search for this author inPubMed Google Scholar * Chuanzhen Lu View

author publications You can also search for this author inPubMed Google Scholar * Jingwu Z Zhang View author publications You can also search for this author inPubMed Google Scholar * Gang

Pei View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Y.S. designed and did the experiments and prepared the manuscript; Y.F. and J.K.

designed and did the experiments and analyzed the data; C.L. assisted with cell purification, activation and culture; Z.L., Z.G. and C.L. provided the blood samples from patients with

multiple sclerosis; D.L. prepared the manuscript; W.C. and J.Q. assisted with the induction of EAE; E.B. and L.Z. assisted with cell purification, activation and culture; and J.Z.Z. and G.P.

supervised all studies and the preparation of the manuscript. CORRESPONDING AUTHORS Correspondence to Jingwu Z Zhang or Gang Pei. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare

no competing financial interests. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–7 and Supplementary Methods (PDF 2619 kb) RIGHTS AND PERMISSIONS Reprints

and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Shi, Y., Feng, Y., Kang, J. _et al._ Critical regulation of CD4+ T cell survival and autoimmunity by β-arrestin 1. _Nat Immunol_ 8,

817–824 (2007). https://doi.org/10.1038/ni1489 Download citation * Received: 29 March 2007 * Accepted: 15 June 2007 * Published: 08 July 2007 * Issue Date: August 2007 * DOI:

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