A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins
A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins
复制标题
DOI：
10.4049/jimmunol.176.4.2161
复制
发表时间：
2006-02-15
影响因子：
4.4
通讯作者：
Beaty, SR
中科院分区：
文献类型：
--
作者：
Sung, SSJ;Fu, SM;Beaty, SR
树突状细胞（DC）介导气道抗原呈递，在哮喘和感染中起关键作用。虽然已知DC亚群执行不同的功能，但它们在小鼠肺中的发生尚未明确定义。在本研究中，发现了三种主要的肺DC群，其中两种是髓样和浆细胞样DC（PDC），它们在其他淋巴器官中具有很好的特征。第三个也是最大的DC群体是整合素α（E）（CD 103）β（7）阳性和I-A（高）CD 11 C（高）-DC群体。发现该群体存在于肺粘膜和血管壁中，表达多种粘附和共刺激分子，贪婪地内吞，有效地呈递Ag，并产生IL-12。整合素α（E）β（7）（+）DC（α E-DC）与上皮内淋巴细胞不同，在表面标志物表型、细胞功能和组织定位方面与CD 11b（高）髓样和mPDCA-1+B220（+）Gr-1（+）PDC群体不同。重要的是，该上皮DC群体表达高水平的朗格汉斯细胞标记物Langerin和紧密连接蛋白Claudin-1、Claudin-7和ZO-2。在诱导气道高反应性和嗜酸性粒细胞增多的小鼠中，肺中aE-DC数量增加，其共刺激分子和粘附分子上调。这些研究表明，aE-DC是主要的和独特的肺DC群体，并且是主要的候选APC，其具有迁移穿过气道上皮用于Ag和病原体捕获、运输和呈递的必需表面蛋白。它们在变应原诱导的肺部炎症中表现出活化的表型，并可能在哮喘发病机制中发挥重要作用。
Dendritic cells (DC) mediate airway Ag presentation and play key roles in asthma and infections. Although DC subsets are known to perform different functions, their occurrence in mouse lungs has not been clearly defined. In this study, three major lung DC populations have been found. Two of them are the myeloid and plasmacytoid DC (PDC) well-characterized in other lymphoid organs. The third and largest DC population is the integrin alpha(E) (CD103) beta(7)-positive and I-A(high)CD11C(high)-DC population. This population was found to reside in the lung mucosa and the vascular wall, express a wide variety of adhesion and costimulation molecules, endocytose avidly, present Ag efficiently, and produce IL-12. Integrin alpha(E)beta(7)(+) DC (alpha E-DC) were distinct from intraepithelial lymphocytes and distinguishable from CD11b(high) myeloid and mPDCA-1+B220(+)Gr-1(+) PDC populations in surface marker phenotype, cellular functions, and tissue localization. Importantly, this epithelial DC population expressed high levels of the Langerhans cell marker Langerin and the tight junction proteins Claudin-1, Claudin-7, and ZO-2. In mice with induced airway hyperresponsiveness and eosinophilia, aE-DC numbers were increased in lungs, and their costimulation and adhesion molecules were up-regulated. These studies show that aE-DC is a major and distinct lung DC population and a prime candidate APC with the requisite surface proteins for migrating across the airway epithelia for Ag and pathogen capture, transport, and presentation.. They exhibit an activated phenotype in allergen-induced lung inflammation and may play significant roles in asthma pathogenesis.