Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.
Department of Pathology, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada; Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, NS, Canada.
Cytokine Growth Factor Rev. 2019 Dec;50:43-51. doi: 10.1016/j.cytogfr.2019.04.003. Epub 2019 Apr 2.
Type I interferons are effector cytokines essential for the regulation of the innate immunity. A key effector of the type I interferon response that is dysregulated in autoimmunity and cancer is the cGAS-STING signalling axis. Recent work suggests that calcium and associated signalling proteins can regulate both cGAS-STING and autoimmunity. How calcium regulates STING activation is complex and involves both stimulatory and inhibitory mechanisms. One of these is calmodulin-mediated signalling that is necessary for STING activation. The alterations in calcium flux that occur during STING activation can also regulate autophagy, which in turn plays a role in innate immunity through the clearance of intracellular pathogens. Also connected to calcium signalling pathways is the cGAS inhibitor TREX1, a cytoplasmic exonuclease linked to several autoimmune diseases including systemic lupus erythematosus (SLE). In this review, we summarize these and other findings that indicate a regulatory role for calcium signalling in innate and autoimmunity through the cGAS-STING pathway.
I 型干扰素是调节先天免疫的必需效应细胞因子。在自身免疫和癌症中失调的 I 型干扰素反应的关键效应物是 cGAS-STING 信号轴。最近的工作表明，钙和相关信号蛋白可以调节 cGAS-STING 和自身免疫。钙如何调节 STING 激活是复杂的，涉及刺激和抑制机制。其中之一是钙调蛋白介导的信号通路，这是 STING 激活所必需的。在 STING 激活过程中发生的钙通量变化也可以调节自噬，自噬通过清除细胞内病原体在先天免疫中发挥作用。与钙信号通路相关的还有 cGAS 抑制剂 TREX1，它是一种细胞质核酸外切酶，与包括系统性红斑狼疮（SLE）在内的几种自身免疫性疾病有关。在这篇综述中，我们总结了这些和其他发现，表明钙信号通过 cGAS-STING 途径在先天免疫和自身免疫中具有调节作用。
