过敏性气道疾病中的m6A修饰：从细胞视角的叙述性综述

文献信息

中文摘要

N6-甲基腺苷（m6A）是真核生物RNA上最常见的修饰，在RNA表达调控的几乎各个阶段均发挥关键作用。大量研究表明，m6A修饰失调在上皮屏障破坏、氧化应激诱导、炎症细胞活化及气道重塑中起重要作用，而这些都是过敏性气道疾病（AADs）的特征性病理表现。鉴于不同细胞类型在AADs进展与缓解中具有不同作用，理解m6A在不同细胞背景下的功能对于全面认识该疾病的病理机制至关重要。本综述首先概述m6A修饰的基本生物学特征。随后，我们从气道上皮细胞、固有免疫细胞和适应性免疫细胞的角度探讨动态m6A修饰如何影响AADs进展，强调m6A在上皮-免疫交互对话中的关键调控作用。接着，我们总结细胞背景如何塑造m6A修饰的功能异质性，并讨论潜在的底层机制。最后，我们总结将m6A相关酶用作疾病预测、治疗干预及评估过敏原免疫治疗疗效工具的最新进展，并讨论m6A靶向治疗策略临床转化所面临的机遇与挑战。

英文摘要

N6-methyladenosine (m6A) represents the most prevalent modification on eukaryotic RNA and plays a critical role in nearly all stages of RNA expression regulation. Extensive research demonstrates that the dysregulation of m6A modification plays a significant role in the disruption of epithelial barriers, the induction of oxidative stress, the activation of inflammatory cells, and the remodeling of airways, all of which are characteristic pathological features of allergic airway diseases (AADs). Given the distinct roles of various cell types in the progression and resolution of AADs, understanding how m6A functions across cellular contexts is essential for a comprehensive understanding of the disease's pathological mechanisms. This review begins by outlining the fundamental biological characteristics of m6A modification. Subsequently, we explore how dynamic m6A modifications affect AADs progression from the perspectives of airway epithelial cells, innate immune cells, and adaptive immune cells, emphasizing the pivotal regulatory role of m6A in epithelial-immune crosstalk. We then summarize how cellular context shapes the functional heterogeneity of m6A modification and discuss the potential underlying mechanisms. Finally, we summarize the latest progress in the use of m6A-related enzymes as tools for disease prediction, therapeutic intervention, and evaluation of allergen immunotherapy efficacy, and discuss the opportunities and challenges associated with the clinical translation of m6A-targeted therapeutic strategies.