嗜酸性粒细胞调控网络在ECRS发生发展中的机制研究

Research on the mechanism of eosinophil regulatory networks in the pathogenesis and progression of ECRS

摘要:

嗜酸性粒细胞型慢性鼻-鼻窦炎(ECRS)是一种以Th2型炎症反应为主、异质性强且复发率高的难治性鼻腔炎症性疾病。嗜酸性粒细胞是其病理过程中的核心效应细胞，其分化、成熟及功能异常是ECRS发生发展的关键。在骨髓中，白介素(IL)-5通过JAK-STAT信号轴介导嗜酸性粒细胞祖细胞的“转运扩增”，是外周血嗜酸性粒细胞数量的关键决定因素；CCAAT/增强子结合蛋白(C/EBP)家族与GATA转录因子程序性协同与制约，共同决定嗜酸性粒细胞的谱系定型。在外周募集阶段，IL-5通过激活β2整合素促进嗜酸性粒细胞穿越内皮，而趋化因子是介导其向鼻黏膜定向迁移的主要通路。在ECRS鼻黏膜局部，2型固有淋巴细胞与Th2细胞形成正反馈环路，释放IL-5，不仅通过抑制Bid延长嗜酸性粒细胞存活时间，还激活其释放颗粒蛋白等产物，加重组织重塑与炎症损伤。本文系统综述了调控嗜酸性粒细胞谱系定型、骨髓内分化成熟、外周募集及鼻腔局部活化的调控网络，并探讨该网络在ECRS发病机制中的作用，旨在为寻找ECRS临床治疗新靶点提供理论依据。

Abstract:

Eosinophilic chronic rhinosinusitis (ECRS) is a refractory nasal inflammatory disease characterized by a Th2-type inflammatory response, high heterogeneity, and high recurrence rate. Eosinophils play a central role in the pathological process of ECRS, and their abnormal differentiation, maturation, and functional alterations are the key factors for the occurrence and development of ECRS. In the bone marrow, interleukin(IL)-5 mediates the "transit amplification" of eosinophil progenitor cells through the JAK-STAT signaling axis, which is a critical determinant of the number of peripheral blood eosinophils. The CCAAT/enhancer binding protein (C/EBP) family and GATA transcription factors coordinately and antagonistically regulate eosinophil lineage commitment. During peripheral recruitment, IL-5 promotes the migration of eosinophils across the endothelium by activating β2 integrins, while chemokines are the primary pathways directing their migration to the nasal mucosa. In the local nasal mucosa of ECRS, type 2 innate lymphoid cells (ILC2s) and Th2 cells form a positive feedback loop to release IL-5. It not only the survival of eosinophils by blocking Bid, but also activates the release of granule proteins and other products, exacerbating tissue remodeling and inflammatory injury. This review systematically summarizes the regulatory networks governing the differentiation and maturation of the eosinophilic cell lineage in the bone marrow, the peripheral recruitment, and the local activation in the nasal cavity. It also explores the role of the network in the pathogenesis of ECRS. The aim is to provide a theoretical basis for the search for new therapeutic targets for ECRS in clinical practice.