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The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases

Acta Pharmacologica Sinica volume 45, pages 1997–2010 (2024)Cite this article

Abstract

Pattern recognition receptors are an essential part of the immune system, which detect pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) and help shape both innate and adaptive immune responses. When dsDNA is present, cyclic GMP-AMP Synthase (cGAS) produces a second messenger called cyclic GMP-AMP (cGAMP), which then triggers an adaptor protein called STING, and eventually activates the expression of type I interferon (IFN) and pro-inflammatory cytokines in immune cells. The cGAS-STING signaling pathway has been receiving a lot of attention lately as a key immune-surveillance mediator. In this review, we summarize the present circumstances of the cGAS-STING signaling pathway in viral infections and inflammatory diseases, as well as autoimmune diseases. Modulation of the cGAS-STING signaling pathway provides potential strategies for treating viral infections, inflammatory diseases, and autoimmune diseases.

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Fig. 1: cGAS-STING and related diseases.
Fig. 2: Structural insights and signal transduction mechanisms of cGAS and STING.
Fig. 3: The cGAS-STING signaling pathway.
Fig. 4: SARS-CoV-2 proteins inhibit the cGAS-STING signaling pathway.
Fig. 5: The dual role of type I interferon (IFN) in COVID-19.
Fig. 6: The double edge effect of cGAS-STING signaling pathway in inflammatory bowel disease.
Fig. 7: Therapeutic targeting of cGAS-STING.

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Acknowledgements

This work was supported by Macau Science and Technology Development Fund, 0058/2020/A, 0018/2023/AMJ, 011/AIJ/2020 and 0003/2021/ AKP; Swedish Research Council (Vetenskapsrådet) 2019–01884; Swedish Cancer Foundation (Cancerfonden) 20 0680 Pj; CIMED FoUI-975445.

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  1. These authors contributed equally: Ming-ming Wang, Yue Zhao, Juan Liu

Authors and Affiliations

  1. State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macao, 999078, China

    Ming-ming Wang, Yue Zhao, Juan Liu, Yan-qing Tang, Zheng-yang Guo & Ting Li

  2. Department of Biosciences and Nutrition, Karolinska Institute, Huddinge, 14183, Sweden

    Rong-rong Fan

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  1. Ming-ming Wang
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Wang, Mm., Zhao, Y., Liu, J. et al. The role of the cGAS-STING signaling pathway in viral infections, inflammatory and autoimmune diseases. Acta Pharmacol Sin 45, 1997–2010 (2024). https://doi.org/10.1038/s41401-023-01185-5

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