Linbin Zhou, Bo Man Ho, Hoi Ying Emily Chan, Yan Tong, Lin Du, Jing Na He, Danny Siu-Chun Ng, Clement C Tham, Chi Pui Pang, Wai Kit Chu
{"title":"cGAS-STING信号在介导眼部炎症中的新作用。","authors":"Linbin Zhou, Bo Man Ho, Hoi Ying Emily Chan, Yan Tong, Lin Du, Jing Na He, Danny Siu-Chun Ng, Clement C Tham, Chi Pui Pang, Wai Kit Chu","doi":"10.1159/000533897","DOIUrl":null,"url":null,"abstract":"<p><p>Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.</p>","PeriodicalId":16113,"journal":{"name":"Journal of Innate Immunity","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616671/pdf/","citationCount":"0","resultStr":"{\"title\":\"Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.\",\"authors\":\"Linbin Zhou, Bo Man Ho, Hoi Ying Emily Chan, Yan Tong, Lin Du, Jing Na He, Danny Siu-Chun Ng, Clement C Tham, Chi Pui Pang, Wai Kit Chu\",\"doi\":\"10.1159/000533897\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.</p>\",\"PeriodicalId\":16113,\"journal\":{\"name\":\"Journal of Innate Immunity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10616671/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Innate Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000533897\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/10/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Innate Immunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000533897","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/10/3 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Emerging Roles of cGAS-STING Signaling in Mediating Ocular Inflammation.
Cyclic GMP-AMP (cGAMP) synthase (cGAS), a sensor of cytosolic DNA, recognizes cytoplasmic nucleic acids to activate the innate immune responses via generation of the second messenger cGAMP and subsequent activation of the stimulator of interferon genes (STINGs). The cGAS-STING signaling has multiple immunologic and physiological functions in all human vital organs. It mediates protective innate immune defense against DNA-containing pathogen infection, confers intrinsic antitumor immunity via detecting tumor-derived DNA, and gives rise to autoimmune and inflammatory diseases upon aberrant activation by cytosolic leakage of self-genomic and mitochondrial DNA. Disruptions in these functions are associated with the pathophysiology of various immunologic and neurodegenerative diseases. Recent evidence indicates important roles of the cGAS-STING signaling in mediating inflammatory responses in ocular inflammatory and inflammation-associated diseases, such as keratitis, diabetic retinopathy, age-related macular degeneration, and uveitis. In this review, we summarize the recently emerging evidence of cGAS-STING signaling in mediating ocular inflammatory responses and affecting pathogenesis of these complex eye diseases. We attempt to provide insightful perspectives on future directions of investigating cGAS-STING signaling in ocular inflammation. Understanding how cGAS-STING signaling is modulated to mediate ocular inflammatory responses would allow future development of novel therapeutic strategies to treat ocular inflammation and autoimmunity.
期刊介绍:
The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.