An emerging role for calcium signalling in innate and autoimmunity via the cGAS-STING axis |
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Affiliation: | 1. Department of Biomedicine, University of Aarhus, Aarhus, Denmark;2. Aarhus Research Center for Innate Immunology, University of Aarhus, Aarhus, Denmark |
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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. |
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Keywords: | STING SLE TREX1 cGAS Calcium signalling Innate immunity Type I interferon response |
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