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

Sabateeshan Mathavarajah; Jayme Salsman; Graham Dellaire

doi:10.1016/j.cytogfr.2019.04.003

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

Sabateeshan Mathavarajah, Jayme Salsman, Graham Dellaire

Résultat de recherche: Short survey › examen par les pairs

39 Citations (Scopus)

Résumé

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.

Langue d'origine	English
Pages (de-à)	43-51
Nombre de pages	9
Journal	Cytokine and Growth Factor Reviews
Volume	50
DOI	https://doi.org/10.1016/j.cytogfr.2019.04.003
Statut de publication	Published - déc. 2019

Note bibliographique

Funding Information:
The authors would like to thank Dr. Danton H. O’Day for critically reviewing the manuscript prior to submission. This work was supported by a Discovery Grant ( RGPIN-05616 ) from the Natural Sciences and Engineering Research Council of Canada (NSERC) to G.D., and S.M. is supported by a CGSM studentship from NSERC, a Predoctoral Fellowship from the Killam Trusts, and a Scotia Scholar award from the Nova Scotia Health Research Foundation.

Publisher Copyright:
© 2019 Elsevier Ltd

ASJC Scopus Subject Areas

Endocrinology, Diabetes and Metabolism
Immunology and Allergy
Immunology
General Biochemistry,Genetics and Molecular Biology

PubMed: MeSH publication types

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

ODD de l’ONU

Cette action contribue à la réalisation des objectifs de développement durable suivants

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10.1016/j.cytogfr.2019.04.003

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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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N2 - 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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An emerging role for calcium signalling in innate and autoimmunity via the cGAS-STING axis

Résumé

Note bibliographique

ASJC Scopus Subject Areas

PubMed: MeSH publication types

ODD de l’ONU

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