摘要
免疫系统由先天性免疫和适应性免疫组成。先天免疫反应作为机体免疫防御的第一道防线,能通过模式识别受体(pattern recognition receptors,PRRs)迅速识别入侵体内的病原体及组织或细胞受到损伤、低氧等因素刺激后释放的内源性损伤相关分子模式(damage-associated molecular patterns,DAMPs),进而产生快速而非特异性的免疫应答[1]。
Mitochondrial DNA(mtDNA),which acts as a immune stimulant,could induce the host immune response. mtDNA released into the cytosol is recognized by cyclic guanosine monophosphate(GMP)-adenosine monophosphate(AMP)synthase(cGAS),a critical cytosolic DNA sensor. Subsequently,a second messenger cyclic GMP-AMP(cGAMP),which was produced by activated cGAS,binds to stimulator of interferon genes(STING)and induces type I interferon-mediated immune response. Activation of cGAS-STING signaling pathway could trigger immune responses and promote inflammatory response,which contributes to the pathogenesis of infections,cancer and autoimmune diseases.Emerging evidence also indicates that release of mtDNA promotes the development of inflammatory lung diseases,which may be related to the disorder of cGAS-STING signaling pathway. This review summarizes and analyzes the studies on release and function of mtDNA,relationship between mtDNA and cGAS-STING pathway,the effect on lung inflammatory diseases,and the inhibitors targeting cGAS-STING signaling pathway,which may reveal the mechanism underlying the pathogenesis of inflammatory pulmonary diseases and provide new insights to potential therapeutic targets.
作者
甄宁新
崔巍
田宝平
ZHEN Ning-xin;CUI Wei;TIAN Bao-ping(Department of Critical Care Medicine,The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310009,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2022年第1期144-153,共10页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81700023,No.82172163)
浙江省自然科学基金资助项目(No.LY20H010002)。
