A major lung CD103 (αE)-β7 integrin-positive epithelial dendritic cell population expressing Langerin and tight junction proteins

被引:382
作者
Sung, SSJ
Fu, SM
Rose, CE
Gaskin, F
Ju, ST
Beaty, SR
机构
[1] Univ Virginia, Sch Med, Hlth Sci Ctr, Dept Internal Med,Div Rheumatol & Immunol, Charlottesville, VA 22908 USA
[2] Univ Virginia, Sch Med, Hlth Sci Ctr, Dept Psychiat Med,Div Rheumatol & Immunol, Charlottesville, VA 22908 USA
[3] Univ Virginia, Sch Med, Specialized Ctr Res System Lupus Erythematosus, Charlottesville, VA 22908 USA
关键词
D O I
10.4049/jimmunol.176.4.2161
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页码:2161 / 2172
页数:12
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