鼻黏膜中的组织驻留记忆T细胞：过敏性鼻炎慢性化与复发的守门人。

文献信息

中文摘要

背景： 过敏性鼻炎（AR）是一种普遍存在的鼻黏膜2型炎症性疾病，其临床病程的定义与其说是急性发作，不如说是复发和对治愈的明显抵抗。尽管AR传统上被框定为一种系统性、IgE驱动的疾病，但越来越多的证据表明鼻黏膜本身是持久、抗原特异性免疫记忆的场所。组织驻留记忆T（TRM）细胞——非再循环、具有长寿特性的淋巴细胞，驻留在屏障组织中——处于理想位置，将短暂的过敏原暴露转化为持续性炎症。方法：本小型综述综合了人类和临床前证据，表明鼻TRM细胞，包括Th2极化的CD4+亚群和最近描述的一种致病性CD8+亚群（首次在复发性慢性鼻窦炎伴鼻息肉，CRSwNP中表征），构成了AR慢性化和免疫治疗后复发的可信——但仍很大程度上是假设性的——细胞基础。结果：我们提出，2025年发现的表达颗粒酶K（GZMK）的CD8+记忆T细胞驱动复发性气道炎症（Lan等，Nature 2025）为理解AR复发提供了一个可转化的框架。我们注意到，关于纯AR中鼻TRM的直接、高分辨率人类证据仍然有限；因此，我们整合了来自CRSwNP、下气道疾病和动物模型的发现作为可转化的证据基础，并明确标记每个结论是已确立的还是假设性的。结论：我们概述了靶向TRM保留、表型或效应分子如何能够补充过敏原免疫治疗。

英文摘要

Allergic rhinitis (AR) is a pervasive type-2 inflammatory disorder of the nasal mucosa whose clinical course is defined less by acute flares than by recurrence and apparent resistance to cure. Although AR has traditionally been framed as a systemic, IgE-driven disease, a growing body of evidence points to the nasal mucosa itself as a site of durable, antigen-specific immune memory. Tissue-resident memory T (TRM) cells - non-recirculating, longevity-endowed lymphocytes that lodge in barrier tissues - are ideally positioned to convert transient allergen exposure into persistent inflammation. This mini review synthesizes human and preclinical evidence that nasal TRM cells, including Th2-polarized CD4+ subsets and a recently described pathogenic CD8+ subset (first characterized in recurrent chronic rhinosinusitis with nasal polyps, CRSwNP), constitute a credible - but still largely hypothetical - cellular substrate for AR chronicity and post-immunotherapy relapse. We propose that the 2025 discovery of granzyme K (GZMK)-expressing CD8+ memory T cells driving recurrent airway inflammation (Lan et al., Nature 2025) provides a translatable framework for understanding AR relapse. We note that direct, high-resolution human evidence for nasal TRM in pure AR remains limited; accordingly, we integrate findings from CRSwNP, lower-airway disease, and animal models as a translatable evidence base and explicitly flag where each conclusion is established versus hypothetical. We outline how targeting TRM retention, phenotype, or effector molecules could complement allergen immunotherapy.