从鼻细胞学到细胞内型分型：过敏性鼻炎中肥大细胞-嗜酸性粒细胞相互作用与重叠性炎症

文献信息

中文摘要

过敏性鼻炎传统上由过敏原致敏和2型炎症定义，但越来越多的证据表明这一框架不能完全捕捉鼻黏膜的生物学异质性。局部炎症景观反映了上皮细胞、固有和适应性淋巴样群体、肥大细胞、嗜酸性粒细胞、基质成分和血管组分之间的动态相互作用，并且可能与全身生物标志物显著不同。最近的单细胞和多组学研究进一步揭示了疾病相关的上皮分化、基质激活和细胞间通讯的改变，强化了鼻黏膜作为整合免疫生态系统的概念。在此背景下，肥大细胞-嗜酸性粒细胞相互作用似乎特别相关，因为它们的共存和脱颗粒可能表征不同于孤立性嗜酸性粒细胞增多的炎症状态。鼻细胞学提供了这种局部细胞结构的临床可及形态学读数，并表明过敏性鼻炎并不对应于单一的细胞学表达。在一些患者中，已确定的过敏致敏与公认的非过敏性细胞性鼻炎实体共存，包括非过敏性鼻炎伴嗜酸性粒细胞（NARES）、非过敏性鼻炎伴肥大细胞（NARMA）和非过敏性鼻炎伴嗜酸性粒细胞和肥大细胞（NARESMA），从而产生了重叠性鼻炎的概念。这一现象挑战了二元过敏性与非过敏性的分类，并可能导致难以治疗的疾病和不完全的治疗反应。尽管这些疾病分类实体在临床和细胞学上已定义，但它们不应被视为分子内型的同义词。其未来价值可能在于一种细胞学信息指导的内型分型策略，将形态学与局部生物标志物、蛋白质组学、转录组学和单细胞方法相结合。本综述讨论了塑造过敏性鼻炎的细胞参与者及其相互作用、重叠性炎症的生物学和临床相关性，以及鼻细胞学作为临床表型分型和分子内型分型之间接口的潜在作用。

英文摘要

Allergic rhinitis is traditionally defined by allergen sensitization and type 2 inflammation, yet increasing evidence indicates that this framework does not fully capture the biological heterogeneity of the nasal mucosa. The local inflammatory landscape reflects a dynamic interaction among epithelial cells, innate and adaptive lymphoid populations, mast cells, eosinophils, stromal elements, and vascular components, and may diverge substantially from systemic biomarkers. Recent single-cell and multi-omic studies have further revealed disease-associated alterations in epithelial differentiation, stromal activation, and cell-cell communication, reinforcing the concept of the nasal mucosa as an integrated immunological ecosystem. Within this context, mast cell-eosinophil interactions appear particularly relevant, as their coexistence and degranulation may characterize inflammatory states that differ from isolated eosinophilia. Nasal cytology provides a clinically accessible morphological readout of this local cellular architecture and has shown that allergic rhinitis does not correspond to a single cytological expression. In some patients, established allergic sensitization coexists with recognized non-allergic cellular rhinitis entities, including non-allergic rhinitis with eosinophils (NARES), non-allergic rhinitis with mast cells (NARMA), and non-allergic rhinitis with eosinophils and mast cells (NARESMA), giving rise to the concept of overlapping rhinitis. This phenomenon challenges a binary allergic versus non-allergic classification and may contribute to difficult-to-treat disease and incomplete therapeutic responses. Although these nosological entities are clinically and cytologically defined, they should not be considered synonymous with molecular endotypes. Their future value may instead lie in a cytology-informed endotyping strategy integrating morphology with local biomarkers, proteomics, transcriptomics, and single-cell approaches. This Review discusses the cellular players and interactions shaping allergic rhinitis, the biological and clinical relevance of overlapping inflammation, and the potential role of nasal cytology as an interface between clinical phenotyping and molecular endotyping.