An emerging role for calcium signalling in innate and autoimmunity via the cGAS-STING axis. (December 2019)

• Record Type: Journal Article
• Authors: Mathavarajah, Sabateeshan; Salsman, Jayme; Dellaire, Graham
• Is Part Of: Cytokine & growth factor reviews. Volume 50(2019)
• Page Start: 43
• Page End: 51
• Publication Date: 2019-12
• Subjects: STING stimulator of IFN genes -- TREX1/2 three prime repair exonuclease 1/2 -- SLE systemic lupus erythematosus -- cGAS cyclic GMP-AMP synthase -- IFN interferon -- Ca2+ calcium; STING -- SLE -- TREX1 -- cGAS -- Calcium signalling -- Innate immunity -- Type I interferon response; Cytokines -- Periodicals; 571.84
• DOI: 10.1016/j.cytogfr.2019.04.003
• Languages: English
• ISSNs: 1359-6101

Abstract

Highlights: Calcium signalling plays a role in innate and autoimmunity via the cGAS-STING axis. During STING activation, TREX1 acts as a brake and cGAS the acceleration pedal. Systemic lupus erythematosus (SLE) pathology is coupled to Ca 2+ homeostasis. STING and STIM1 connect Ca 2+ homeostasis to type I interferon signaling. AMPK activation by STING links autophagy to the IFN response and relies on Ca 2+ signaling. Abstract: 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.