Shanghai Key Laboratory of Signalling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, China.
Immunology. 2013 Dec;140(4):430-40. doi: 10.1111/imm.12152.
β-Arrestins are well-known regulators and mediators of G protein-coupled receptor signalling, and accumulating evidence reveals that they are functionally involved in inflammation and autoimmune diseases. Of the two β-arrestins, β-arrestin 1 is documented to play regulatory roles in an animal model of multiple sclerosis (MS), whereas the role of β-arrestin 2 is less clear. Here, we show that β-arrestin 2-deficient mice displayed the exacerbated and sustained symptoms of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. At the cellular level, deficiency of β-arrestin 2 led to a decreased number of Foxp3(+) CD4(+) regulatory T (Treg) cells in peripheral lymphoid organs of EAE mice. Consistently, our in vitro observations also revealed that loss of β-arrestin 2 impaired the conversion of Foxp3(-) CD4(+) T cells into Foxp3(+) CD4(+) inducible Treg cells. Taken together, our data suggest that β-arrestin 2 plays a regulatory role in MS, that is opposite to that of β-arrestin 1, in autoimmune diseases such as MS, which is at least partially through regulation of iTreg cell differentiation.
β- arrestins 是 G 蛋白偶联受体信号的著名调节剂和介质，越来越多的证据表明它们在炎症和自身免疫性疾病中具有功能作用。在两种β-arrestins 中，β-arrestin 1 被证明在多发性硬化症（MS）的动物模型中发挥调节作用，而β-arrestin 2 的作用则不太清楚。在这里，我们显示β-arrestin 2 缺陷小鼠表现出实验性自身免疫性脑脊髓炎（EAE）的症状加重和持续，EAE 是 MS 的动物模型。在细胞水平上，β-arrestin 2 的缺乏导致 EAE 小鼠外周淋巴器官中 Foxp3(+) CD4(+) 调节性 T（Treg）细胞数量减少。一致地，我们的体外观察也表明，β-arrestin 2 的缺失损害了 Foxp3(-) CD4(+) T 细胞向 Foxp3(+) CD4(+) 诱导性 Treg 细胞的转化。总之，我们的数据表明，β-arrestin 2 在多发性硬化症等自身免疫性疾病中发挥调节作用，与β-arrestin 1 的作用相反，至少部分是通过调节 iTreg 细胞分化来实现的。
