Ealey Kafi N, Moro Kazuyo, Koyasu Shigeo
Laboratory for Innate Immune Systems, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan.
Immunol Rev. 2017 Jul;278(1):207-218. doi: 10.1111/imr.12547.
Asthma is a complex heterogeneous disease of the airways characterized by lung inflammation, airway hyperreactivity (AHR), mucus overproduction, and remodeling of the airways. Group 2 innate lymphoid cells (ILC2s) play a crucial role in the initiation and propagation of type 2 inflammatory programs in allergic asthma models, independent of adaptive immunity. In response to allergen, helminths or viral infection, damaged airway epithelial cells secrete IL-33, IL-25, and thymic stromal lymphopoietin (TSLP), which activate ILC2s to produce type 2 cytokines such as IL-5, IL-13, and IL-9. Furthermore, ILC2s coordinate a network of cellular responses and interact with numerous cell types to propagate the inflammatory response and repair lung damage. ILC2s display functional plasticity in distinct asthma phenotypes, enabling them to respond to very different immune microenvironments. Thus, in the context of non-allergic asthma, triggered by exposure to environmental factors, ILC2s transdifferentiate to ILC1-like cells and activate type 1 inflammatory programs in the lung. In this review, we summarize accumulating evidence on the heterogeneity, plasticity, regulatory mechanisms, and pleiotropic roles of ILC2s in allergic inflammation as well as mechanisms for their suppression in the airways.
哮喘是一种复杂的气道异质性疾病，其特征为肺部炎症、气道高反应性（AHR）、黏液过度产生以及气道重塑。2型固有淋巴细胞（ILC2s）在过敏性哮喘模型中2型炎症程序的启动和传播中起着关键作用，独立于适应性免疫。响应过敏原、蠕虫或病毒感染，受损的气道上皮细胞分泌IL-33、IL-25和胸腺基质淋巴细胞生成素（TSLP），这些物质激活ILC2s以产生2型细胞因子，如IL-5、IL-13和IL-9。此外，ILC2s协调细胞反应网络，并与多种细胞类型相互作用，以传播炎症反应并修复肺损伤。ILC2s在不同的哮喘表型中表现出功能可塑性，使其能够对非常不同的免疫微环境做出反应。因此，在由暴露于环境因素引发的非过敏性哮喘背景下，ILC2s转分化为ILC1样细胞并激活肺部的1型炎症程序。在本综述中，我们总结了关于ILC2s在过敏性炎症中的异质性、可塑性、调节机制和多效性作用以及其在气道中被抑制的机制的越来越多的证据。
