A Major Lung CD103 (αE)-β7 Integrin-Positive Epithelial Dendritic Cell Population Expressing Langerin and Tight Junction Proteins

Abstract

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 αE (CD103) β7-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 αEβ7+ DC (αE-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, αE-DC numbers were increased in lungs, and their costimulation and adhesion molecules were up-regulated. These studies show that αE-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.

Origin and functional specializations of DC subsets in the lung

“…In the mouse, intraepithelial CD11b À CD103 1 lung DC have been shown to express claudin-1, claudin-7 and zonula-2 proteins to form tight junctions with neighboring airway epithelial cells. This could explain how DC sample the airway lumen without disturbing the epithelial barrier function [27]. A similar model has been proposed in the gut as well as in the skin, where Langerhans cells extend dendrites just underneath the stratum corneum [28,29].…”

Detection and quantitation of eosinophils in the murine respiratory tract by flow cytometry

“…We chose Siglec-F as a potential marker amenable to this flow-based approach since it has documented to be present on the surface of eosinophils and alveolar macrophages (Sung et al 2006).…”

“…Neither population expressed high levels of MHC II, CD86, or CD40 when compared to the relevant isotype controls, suggesting that these populations did not include conventional Siglec-F − CD11c + dendritic cells (Sung et al 2006) (TS Kim, unpublished observations).…”

Insights into Langerhans cell function from Langerhans cell ablation models

“…Utilizing Langerin-EGFP knockin mice it became apparent that the majority of blood-derived CD8 1 DC in the thymus, spleen, cutaneous LN (CLN) and mesenteric LN also express lower levels of Langerin, depending on the genetic background (Table 2) [30,38,39]. Langerin 1 CD8 À (CD103 1 CD11b À ) DC have also been described in the lung specifically localized at the basal lamina of the bronchial epithelia and arterioles of the lung [40]. Initial studies with the Dutch and French Langerin-DTR-EGFP models demonstrated that DT treatment efficiently ablated LC in the epidermis, as well as LC and blood-derived CD8 1 Langerin lo DC in the CLN.…”

“…Both cell types maintain their phenotype in the skin and CLN. Interestingly, Langerin 1 dDC are phenotypically very similar to Langerin 1 DC populations found in the lung, and it is yet unclear whether these two populations are mutually exclusive or together constitute a Langerin 1 interstitial DC subset [36,40]. Recent experiments demonstrate that clearance of influenza virus from the lung depends on this migratory Langerin 1 DC subset [43].…”