Emerging role of the cGAS-STING signaling pathway in autoimmune diseases: Biologic function,mechanisms and clinical prospection |
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| Institution: | 1. Inflammation and Immune Mediated Diseases Laboratory of Anhui Province; School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China;2. Institute for Liver Diseases of Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China;3. Department of oncology, the First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, Anhui 230022, China;4. Department of Clinical Medical, the First Clinical Medical College, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China;5. First-in-Human Clinical Trial Wards in the National Institute of Clinical Drug Trials, The First Affiliated Hospital of Bengbu Medical University, Bengbu, Anhui, China;6. School of Public Foundation, Bengbu Medical University, Bengbu, Anhui, China;1. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA;1. Department of Rheumatology and Clinical Immunology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China;2. Department of Rheumatology, Guangdong Provincial People''s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China |
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| 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. |
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| Keywords: | type-I interferon |
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