Vroman Heleen, Hendriks Rudi W, Kool Mirjam
Department of Pulmonary Medicine, Erasmus MC, Rotterdam, Netherlands.
Front Immunol. 2017 Aug 9;8:941. doi: 10.3389/fimmu.2017.00941. eCollection 2017.
Asthma is a prevalent chronic heterogeneous inflammatory disease of the airways, leading to reversible airway obstruction, in which various inflammatory responses can be observed. Mild to moderate asthma patients often present with a Th2-mediated eosinophilic inflammation whereas in severe asthma patients, a Th17-associated neutrophilic or combined Th2 and Th17-mediated eosinophilic/neutrophilic inflammation is observed. The differentiation of these effector Th2 and Th17-cells is induced by allergen-exposed dendritic cells (DCs) that migrate toward the lung draining lymph node. The DC lineage comprises conventional DCs (cDCs) and plasmacytoid DCs (pDCs), of which the cDC lineage consists of type 1 cDCs (cDC1s) and cDC2s. During inflammation, also monocytes can differentiate into so-called monocyte-derived DCs (moDCs). These DC subsets differ both in ontogeny, localization, and in their functional properties. New identification tools and the availability of transgenic mice targeting specific DC subsets enable the investigation of how these different DC subsets contribute to or suppress asthma pathogenesis. In this review, we will discuss mechanisms used by different DC subsets to elicit or hamper the pathogenesis of both Th2-mediated eosinophilic asthma and more severe Th17-mediated neutrophilic inflammation.
哮喘是一种常见的慢性异质性气道炎症性疾病，可导致可逆性气道阻塞，其中可观察到多种炎症反应。轻度至中度哮喘患者常表现为Th2介导的嗜酸性粒细胞炎症，而重度哮喘患者则观察到Th17相关的中性粒细胞炎症或Th2和Th17联合介导的嗜酸性粒细胞/中性粒细胞炎症。这些效应性Th2细胞和Th17细胞的分化是由暴露于变应原的树突状细胞（DC）诱导的，这些DC向肺引流淋巴结迁移。DC谱系包括传统DC（cDC）和浆细胞样DC（pDC），其中cDC谱系由1型cDC（cDC1）和cDC2组成。在炎症过程中，单核细胞也可分化为所谓的单核细胞衍生DC（moDC）。这些DC亚群在个体发生、定位及其功能特性方面均有所不同。新的鉴定工具以及针对特定DC亚群的转基因小鼠的可用性，使得研究这些不同的DC亚群如何促进或抑制哮喘发病机制成为可能。在本综述中，我们将讨论不同DC亚群用于引发或阻碍Th2介导的嗜酸性粒细胞性哮喘和更严重的Th17介导的中性粒细胞炎症发病机制的机制。
