Chen Hongyan, Zhang Xiaoting, Su Hao, Zeng Judeng, Chan Hung, Li Qing, Liu Xiaodong, Zhang Lin, Wu William Ka Kei, Chan Matthew Tak Vai, Chen Huarong
Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong, China.
CUHK Shenzhen Research Institute, Shenzhen, Guangdong, China.
Wiley Interdiscip Rev RNA. 2023 May-Jun;14(3):e1764. doi: 10.1002/wrna.1764. Epub 2022 Sep 23.
Sepsis is defined as life-threatening organ dysfunction caused by the host immune dysregulation to infection. It is a highly heterogeneous syndrome with complex pathophysiological mechanisms. The host immune response to sepsis can be divided into hyper-inflammatory and immune-suppressive phases which could exist simultaneously. In the initial stage, systemic immune response is activated after exposure to pathogens. Both innate and adaptive immune cells undergo epigenomic, transcriptomic, and functional reprogramming, resulting in systemic and persistent inflammatory responses. Following the hyper-inflammatory phase, the body is in a state of continuous immunosuppression, which is related to immune cell apoptosis, metabolic failure, and epigenetic reprogramming. Immunosuppression leads to increased susceptibility to secondary infections in patients with sepsis. RNA N6-Methyladenosine (m6A) has been recognized as an indispensable epitranscriptomic modification involved in both physiological and pathological processes. Recent studies suggest that m6A could reprogram both innate and adaptive immune cells through posttranscriptional regulation of RNA metabolism. Dysregulated m6A modifications contribute to the pathogenesis of immune-related diseases. In this review, we summarize immune cell changes and the potential role of m6A modification in sepsis. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > RNA Editing and Modification.
脓毒症被定义为由宿主对感染的免疫失调引起的危及生命的器官功能障碍。它是一种具有复杂病理生理机制的高度异质性综合征。宿主对脓毒症的免疫反应可分为可能同时存在的高炎症期和免疫抑制期。在初始阶段，暴露于病原体后全身免疫反应被激活。先天性和适应性免疫细胞都会经历表观基因组、转录组和功能重编程，导致全身持续性炎症反应。在高炎症期之后，身体处于持续免疫抑制状态，这与免疫细胞凋亡、代谢衰竭和表观遗传重编程有关。免疫抑制导致脓毒症患者继发感染的易感性增加。RNA N6-甲基腺苷（m6A）已被认为是一种不可或缺的表观转录组修饰，参与生理和病理过程。最近的研究表明，m6A可通过对RNA代谢的转录后调控对先天性和适应性免疫细胞进行重编程。m6A修饰失调有助于免疫相关疾病的发病机制。在本综述中，我们总结了脓毒症中免疫细胞的变化以及m6A修饰的潜在作用。本文分类如下：疾病与发育中的RNA>疾病中的RNA；RNA加工>RNA编辑与修饰。
