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The Journal of Immunology, 2006, 176: 2161-2172.
Copyright © 2006 by The American Association of Immunologists

A Major Lung CD103 ({alpha}E)-beta7 Integrin-Positive Epithelial Dendritic Cell Population Expressing Langerin and Tight Junction Proteins1

Sun-Sang J. Sung2,*,{ddagger}, Shu Man Fu*,{ddagger}, C. Edward Rose, Jr.*, Felicia Gaskin{ddagger},{dagger}, Shyr-Te Ju*,{ddagger} and Steven R. Beaty*,{ddagger}

* Department of Internal Medicine and {dagger} Department of Psychiatric Medicine, and {ddagger} University of Virginia Specialized Center of Research in Systemic Lupus Erythematosus, University of Virginia School of Medicine, Charlottesville, VA 22908

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) beta7-positive and I-AhighCD11chigh-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}Ebeta7+ DC ({alpha}E-DC) were distinct from intraepithelial lymphocytes and distinguishable from CD11bhigh 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, {alpha}E-DC numbers were increased in lungs, and their costimulation and adhesion molecules were up-regulated. These studies show that {alpha}E-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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