Table_1_Epigenetic Regulation in Sepsis, Role in Pathophysiology and Therapeutic Perspective.DOCX

Sepsis is characterized by an initial hyperinflammatory response, with intense cell activation and cytokine storm. In parallel, a prolonged compensatory anti-inflammatory response, known as immunological tolerance, can lead to immunosuppression. Clinically, this condition is associated with multiple organ failure, resulting in the patient's death. The mechanisms underlying the pathophysiology of sepsis are not yet fully understood, but evidence is strong showing that epigenetic changes, including DNA methylation and post-translational modifications of histones, modulate the inflammatory response of sepsis. During the onset of infection, host cells undergo epigenetic changes that favor pathogen survival. Besides, epigenetic changes in essential genes also orchestrate the patient's inflammatory response. In this review, we gathered studies on sepsis and epigenetics to show the central role of epigenetic mechanisms in various aspects of the pathogenesis of sepsis and the potential of epigenetic interventions for its treatment.

脓毒症（Sepsis）以初始高炎症反应为特征，伴随强烈的细胞活化与细胞因子风暴（cytokine storm）。与此同时，一种被称为免疫耐受（immunological tolerance）的长期代偿性抗炎反应可引发免疫抑制。临床上，该病症常伴随多器官功能衰竭（multiple organ failure），最终可导致患者死亡。目前，脓毒症病理生理学的潜在机制尚未完全阐明，但已有充分证据表明，包括DNA甲基化（DNA methylation）与组蛋白翻译后修饰（post-translational modifications of histones）在内的表观遗传改变（epigenetic changes）可调控脓毒症的炎症反应。在感染发作期间，宿主细胞会发生有利于病原体存活的表观遗传改变。此外，关键基因的表观遗传改变同样参与调控患者的炎症反应。本综述中，我们整理了脓毒症与表观遗传学相关的研究，旨在阐明表观遗传机制在脓毒症发病机制多个维度的核心作用，以及表观遗传干预手段用于该病治疗的潜在价值。