Institute of Systems Immunology, Julius-Maximilians University of Würzburg, Würzburg, Germany; Department of Pathology, New York University School of Medicine, New York, NY, USA.
Institute of Molecular and Clinical Immunology, Health Campus Immunology, Infectiology, and Inflammation, Otto-von-Guericke University Magdeburg, Magdeburg, Germany; Department of Pathology, New York University School of Medicine, New York, NY, USA.
Trends Immunol. 2020 Oct;41(10):878-901. doi: 10.1016/j.it.2020.06.012. Epub 2020 Jul 22.
Calcium (Ca) signals play fundamental roles in immune cell function. The main sources of Ca influx in mammalian lymphocytes following antigen receptor stimulation are Ca release-activated Ca (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 Ca 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.
钙 (Ca) 信号在免疫细胞功能中发挥着重要作用。在哺乳动物淋巴细胞中，抗原受体刺激后 Ca 内流的主要来源是 Ca 释放激活的 Ca（CRAC）通道。这些通道由质膜中的 ORAI 蛋白形成，并由内质网 (ER) 中定位的基质相互作用分子 (STIM) 激活。人类 ORAI1 和 STIM1 的功能丧失 (LOF) 突变会消除 Ca 内流，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、自身免疫和非免疫性症状。缺乏 Stim 和 Orai 基因的小鼠研究阐明了这些分子控制淋巴细胞功能的许多细胞和分子机制。CRAC 通道对于提供抗感染免疫、介导炎症和预防自身免疫的几种 T 淋巴细胞亚群的分化和功能是必需的。这篇综述探讨了 CRAC 通道如何控制 T 细胞介导的免疫的新见解。
