TREX1介导的免疫调控机制及其在脓毒症中的作用研究进展

Mechanism of TREX1-mediated immune regulation and its role in sepsis

脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍。脓毒症引起的细胞裂解和坏死,线粒体DNA(mtDNA)和核DNA(nDNA)将被动释放到循环,并通过与模式识别受体(PRR)结合,促进大量炎症细胞因子的产生,增加病死率。三素修复核酸外切酶1(TREX1)是一种3'端—5'端核酸外切酶,通过切割磷酸二酯键来快速降解单链DNA(ssDNA)和双链DNA(dsDNA),防止损伤DNA在细胞质内蓄积,引起异常炎症和病理性免疫反应,这在一定程度上对调节脓毒症引起DNA相关的损伤发挥重要的调节作用,但TREX1在脓毒症中的作用与潜在机制尚缺乏深入地讨论,本文就TREX1的结构与功能及其介导的免疫调控机制进行综述,以期阐述TREX1在脓毒症领域中可能发挥的作用。

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.Sepsis-induced cell lysis and necrosis lead to the passive release of mitochondrial DNA(mtDNA)and nuclear DNA(nDNA)into circulation.These DNAs bind to pattern recognition receptor(PRR),triggering excessive inflammatory cytokines production and increasing mortality.Three prime repair exonuclease 1(TREX1)is a 3'to 5'exonuclease that rapidly degrades single-stranded DNA(ssDNA)and double-stranded DNA(dsDNA)by cleaving phosphodiester bonds.This process can prevent the accumulation of damaged DNA in the cytoplasm,thereby averting abnormal inflammation and pathological immune responses.TREX1 thus plays a significant role in regulating DNA-related damage caused by sepsis.However,the role and underlying mechanisms of TREX1 in sepsis have not been thoroughly discussed.This review aims to elucidate the structure and function of TREX1 and its mediated immune regulatory mechanisms,with the hope of clarifying the potential role of TREX1 in the field of sepsis.