An emerging role for calcium signalling in innate and autoimmunity via the cGAS-STING axis

Cytokine Growth Factor Rev. 2019 Dec:50:43-51. doi: 10.1016/j.cytogfr.2019.04.003. Epub 2019 Apr 2.

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.

Keywords: Calcium signalling; Innate immunity; SLE; STING; TREX1; Type I interferon response; cGAS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmunity*
  • Autophagy
  • Calcium / metabolism*
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Innate*
  • Interferon Type I / genetics
  • Interferon Type I / immunology
  • Lupus Erythematosus, Systemic / immunology
  • Membrane Proteins / immunology*
  • Mice
  • Nucleotidyltransferases / immunology*
  • Signal Transduction*

Substances

  • Interferon Type I
  • Membrane Proteins
  • STING1 protein, human
  • Nucleotidyltransferases
  • cGAS protein, human
  • Calcium