Department of Pathology, New York University Langone Medical Center, New York, USA.
Ann N Y Acad Sci. 2011 Nov;1238:74-90. doi: 10.1111/j.1749-6632.2011.06240.x.
Mutations in genes encoding the calcium-release activated calcium (CRAC) channel abolish calcium influx in cells of the immune system and cause severe congenital immunodeficiency. Patients with autosomal recessive mutations in the CRAC channel gene ORAI1, its activator stromal interaction molecule 1 (STIM1), and mice with targeted deletion of Orai1, Stim1, and Stim2 genes reveal important roles for CRAC channels in adaptive and innate immune responses to infection and in autoimmunity. Because CRAC channels have important functions outside the immune system, deficiency of either ORAI1 or STIM1 is associated with a unique clinical phenotype. This review will give an overview of CRAC channel function in the immune system, examine the consequences of CRAC channel deficiency for immunity in human patients and mice, and discuss genetic defects in immunoreceptor-associated signaling molecules that compromise calcium influx and cause immunodeficiency.
基因突变会导致钙释放激活钙（CRAC）通道的编码基因失活，从而使免疫系统的细胞无法摄取钙离子，引发严重的先天性免疫缺陷。患有常染色体隐性遗传基因突变的 CRAC 通道基因 ORAl1、其激活剂基质相互作用分子 1（STIM1）的患者，以及靶向敲除 Orai1、Stim1 和 Stim2 基因的小鼠，揭示了 CRAC 通道在感染和自身免疫中的适应性和先天免疫反应中的重要作用。由于 CRAC 通道在免疫系统外具有重要功能，因此 ORAI1 或 STIM1 的缺乏与独特的临床表型相关。这篇综述将概述 CRAC 通道在免疫系统中的功能，检查 CRAC 通道缺陷对人类患者和小鼠免疫的影响，并讨论免疫受体相关信号分子的遗传缺陷如何导致钙内流受损和免疫缺陷。
