Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function, mechanisms and clinical prospection.
Autoimmun Rev
; 21(9): 103155, 2022 Sep.
Article
in English
| MEDLINE | ID: covidwho-2003879
ABSTRACT
The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) signaling pathway, as vital component of innate immune system, acts a vital role in distinguishing invasive pathogens and cytosolic DNA. Cytosolic DNA sensor cGAS first binds to cytosolic DNA and catalyzes synthesis of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), which is known as the second messenger. Next, cGAMP activates the adaptor protein STING, triggering a molecular chain reaction to stimulate cytokines including interferons (IFNs). Recently, many researches have revealed that the regulatory role of cGAS-STING signaling pathway in autoimmune diseases (AIDs) such as Rheumatoid arthritis (RA), Aicardi Goutières syndrome (AGS) and systemic lupus erythematosus (SLE). Moreover, accumulated evidence have showed inhibition of the cGAS-STING signaling pathway could remarkably suppress the joint swelling and inflammatory cell infiltration in RA mice. Therefore, in this review, we describe the molecular properties, biologic function and mechanisms of the cGAS-STING signaling pathway in AIDs. In addition, potential clinical applications especially selective small molecule inhibitors targeting the cGAS-STING signaling pathway are also discussed.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Autoimmune Diseases
/
Biological Products
/
Acquired Immunodeficiency Syndrome
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Autoimmun Rev
Journal subject:
Allergy and Immunology
Year:
2022
Document Type:
Article
Affiliation country:
J.autrev.2022.103155
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