Trends in Immunology ( IF 16.8 ) Pub Date : 2020-07-22 , DOI: 10.1016/j.it.2020.06.012 Martin Vaeth 1 , Sascha Kahlfuss 2 , Stefan Feske 3
Calcium (Ca2+) signals play fundamental roles in immune cell function. The main sources of Ca2+ influx in mammalian lymphocytes following antigen receptor stimulation are Ca2+ release-activated Ca2+ (CRAC) channels. These are formed by ORAI proteins in the plasma membrane and are activated by stromal interaction molecules (STIM) located in the endoplasmic reticulum (ER). Human loss-of-function (LOF) mutations in ORAI1 and STIM1 that abolish Ca2+ influx cause a unique disease syndrome called CRAC channelopathy that is characterized by immunodeficiency autoimmunity and non-immunological symptoms. Studies in mice lacking Stim and Orai genes have illuminated many cellular and molecular mechanisms by which these molecules control lymphocyte function. CRAC channels are required for the differentiation and function of several T lymphocyte subsets that provide immunity to infection, mediate inflammation and prevent autoimmunity. This review examines new insights into how CRAC channels control T cell-mediated immunity.
中文翻译:
T细胞介导的免疫中的CRAC通道和钙信号传导。
钙(Ca 2+)信号在免疫细胞功能中起基本作用。抗原受体刺激后,哺乳动物淋巴细胞中Ca 2+流入的主要来源是Ca 2+释放激活的Ca 2+(CRAC)通道。它们由质膜中的ORAI蛋白形成,并由位于内质网(ER)中的基质相互作用分子(STIM)激活。废除Ca 2+流入的ORAI1和STIM1中的人类功能丧失(LOF)突变会导致一种称为CRAC通道病的独特疾病综合征,其特征是免疫缺陷性自身免疫和非免疫症状。在缺乏Stim和Orai基因已经阐明了许多细胞和分子机制,这些分子通过这些机制来控制淋巴细胞的功能。CRAC通道是几种T淋巴细胞亚群的分化和功能所必需的,这些亚群可提供对感染的免疫力,介导炎症并预防自身免疫。这篇评论检查了有关CRAC通道如何控制T细胞介导的免疫力的新见解。