Regulation and function of the cGAS-MITA/STING axis in health and disease

Zhi-Dong Zhang; Bo Zhong

doi:10.1016/j.cellin.2021.100001

Regulation and function of the cGAS-MITA/STING axis in health and disease

Cell Insight. 2022 Jan 5;1(1):100001. doi: 10.1016/j.cellin.2021.100001. eCollection 2022 Feb.

Authors

Zhi-Dong Zhang^{1

2

3

4}, Bo Zhong^{1

2

3

5

4}

Affiliations

¹ Department of Gastrointestinal Surgery, Medical Research Institute, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
² Department of Pulmonary and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
³ Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan, 430071, China.
⁴ Wuhan Research Center for Infectious Diseases and Cancer, Chinese Academy of Medical Sciences, Wuhan, 430071, China.
⁵ Department of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Abstract

The innate immune systems detect pathogens via pattern-recognition receptors including nucleic acid sensors and non-nucleic acid sensors. Cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS, also known as MB21D1) is a cytosolic DNA sensor that recognizes double-stranded DNA (dsDNA) and catalyzes the synthesis of 2',3'-cGAMP. Subsequently, 2',3'-cGAMP binds to the adaptor protein mediator of IRF3 activation (MITA, also known as STING, MPYS, ERIS, and TMEM173) to activate downstream signaling cascades. The cGAS-MITA/STING signaling critically mediates immune responses against DNA viruses, retroviruses, bacteria, and protozoan parasites. In addition, recent discoveries have extended our understanding of the roles of the cGAS-MITA/STING pathway in autoimmune diseases and cancers. Here, we summarize the identification and activation of cGAS and MITA/STING, present the updated functions and regulatory mechanisms of cGAS-MITA/STING signaling and provide a comprehensive understanding of the cGAS-MITA/STING axis in autoimmune diseases and cancers.

Keywords: Autoimmune diseases; Cancer; Innate immunity; MITA/STING; cGAS.

Publication types

Review