Critical regulation of CD4⁺ T cell survival and autoimmunity by β-arrestin 1

Nature Immunology 8, 817 - 824 (2007)

Speaker: 謝家漪                            Time: 15:10~16:00, 09/19/ 2007

Commentator: 林以行 老師                  Place: Room 601

Abstract:

     On antigen stimulation, T cells proliferate and differentiate into effector T cells. The number of activated T cells must be controlled via inducing apoptosis to maintain T cell homeostasis. β-arrestin 1 (encoded by Arrb1) has been reported to involve in multiple signaling pathway and its expression is higher in neural and immune systems⁽¹⁾, but the function of β-arrestin 1 in immune cells was mostly unknown.  First, the authors create Arrb1^-/- and Arrb1tg(transgenic) mice to examine lymphoid development and they found that both peripheral naïve and activated CD4⁺ T cells from Arrb1^-/- mice are prone to apoptosis. Secondly, they found that Arrb1 knockdown would downregulate transcription of the antiapoptotic gene Bcl2 by Affymetriz gene chips assay. The expression pattern of Arrb1 and Bcl2 was similar in CD4⁺ T cells activation. Furthermore, they investigated the possible mechanism by which β-arrestin1 could regulate Bcl2 transcription and they found that β-arrestin1 recruited p300, a histone acetyltransferse to promote Bcl2 expression by increasing acetylation of histone H4 at Bcl2 promoter regions. Moreover, the authors used EAE (encephalomyelitis) induced animal model to evaluate the pathophysiological relevance of β-arrestin1 effect on CD4⁺ T cells and they found that β-arrestin1 enhanced the survival of encephalitogenic CD4⁺ T cells and promoted the progression of autoimmune demyelination. The higher expression of β-arrestin1 in CD4⁺ T cells from multiple sclerosis patients was also confirmed the involvement of β-arrestin1 in the increased and activation of inflammatory CD4⁺ T cells. These data indicate an important new function for β-arrestin1 in peripheral CD4⁺ T cells survival and autoimmunity regulation⁽²⁾.

References:

1. Parruti, G. et al. Molecular analysis of human b-arrestin-1: cloning, tissue distribution,and regulation of expression. Identification of two isoforms generated by alternative splicing. J. Biol. Chem. 268, 9753–9761 (1993).

2. Shi, Y. et al. Critical regulation of CD4+ T cell survival and autoimmunity by β-arrestin 1. Nat. Immunol. 8, 817–824 (2007).