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Sci. STKE, 31 July 2007
Vol. 2007, Issue 397, p. tw268
[DOI: 10.1126/stke.3972007tw268]


Immunology An Arrestin Immune Response

Elizabeth M. Adler

Science's STKE, AAAS, Washington, DC 20005, USA

Our survival depends on the elimination of pathogens by the immune system. If not kept in check, however, the immune system can become self-destructive, and dysregulation of the adaptive immune response—for instance, failure to eliminate effector T cells after a pathogen has been cleared—is associated with the development of autoimmune disorders (see Frederick and Miller). Shi et al. found that mice lacking Arrb1, which encodes beta-arrestin-1 (a scaffolding protein identified in terms of its cytoplasmic role in G protein-coupled receptor signaling but since discovered to act in the nucleus as well), had fewer peripheral CD4+ T cells than did wild-type mice. Naive and activated CD4+ T cells from Arrb1–/– mice were more likely to undergo apoptosis than those from wild-type mice, whereas activated CD4+ T cells from Arrb1-transgenic mice (Arrb1tg mice) were less likely to do so. Several days after an immunological challenge, Arrb1–/– mice had a smaller population of responding CD4+ T cells than did wild-type mice, whereas Arrb1tg mice had a larger population. Arrb1 knockdown led to a decrease in transcription of the gene encoding the antiapoptotic protein Bcl-2. After CD4+ T cell activation, Bcl-2 expression tracked that of Arrb1; such dynamic changes in Bcl-2 expression were absent in Arrb1–/– cells. Further analysis indicated that beta-arrestin-1 stimulated Bcl-2 expression through acetylation of histone H4 at the Bcl-2 promoter. Intriguingly, Arrb1–/– mice were less susceptible to experimental autoimmune encephalomyelitis than were wild-type mice, whereas Arrb1tg mice were more susceptible, and CD4+ T cells from people with multiple sclerosis showed increased expression of ARRB1 and BCL2. Moreover, beta-arrestin-1 knockdown in CD4+ T cells directed against myelin basic protein led to a decrease in Bcl-2 and an increased susceptibility to apoptosis. Thus, the authors conclude that beta-arrestin-1 plays a key role in CD4+ T cell homeostasis by regulating the expression of Bcl-2.

Y. Shi, Y. Feng, J. Kang, C. Liu, Z. Li, D. Li, W. Cao, J. Qiu, Z. Guo, E. Bi, L. Zang, C. Lu, J. Z. Zhang, G. Pei, Critical regulation of CD4+ T cell survival and autoimmunity by beta-arrestin 1. Nat. Immunol. 8, 817-824 (2007). [PubMed]

T. J. Frederick, S. D. Miller, Arresting autoimmunity by blocking beta-arrestin 1. Nat. Immunol. 8, 791-792 (2007). [PubMed]

Citation: E. M. Adler, An Arrestin Immune Response. Sci. STKE 2007, tw268 (2007).

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