title: A major lung CD103 (alphaE)-beta7 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 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 (alphaE-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, alphaE-DC numbers were increased in lungs, and their costimulation and adhesion molecules were up-regulated. These studies show that alphaE-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.
authors.affiliation: Department of Internal Medicine, University of Virginia School of Medicine, Charlotteville, 22908, USA.
authors.forename: Sun-Sang J
authors.initials: SS
authors.lastname: Sung
authors.forename: Shu Man
authors.initials: SM
authors.lastname: Fu
authors.forename: C Edward
authors.initials: CE
authors.lastname: Rose
authors.forename: Felicia
authors.initials: F
authors.lastname: Gaskin
authors.forename: Shyr-Te
authors.initials: ST
authors.lastname: Ju
authors.forename: Steven R
authors.initials: SR
authors.lastname: Beaty
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D018122:B7-1 Antigen / Q000378:metabolism; D060890:B7-H1 Antigen; D015415:Biomarkers; D039481:CD11b Antigen / Q000378:metabolism; D002448:Cell Adhesion; D049109:Cell Proliferation; D002478:Cells, Cultured; D062445:Claudin-1; D057167:Claudins; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism; D039001:Integrin alpha Chains / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism*; D018664:Interleukin-12 / Q000096:biosynthesis; D037102:Lectins / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology* / Q000276:immunology; D008264:Macrophages / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013601:T-Lymphocytes / Q000166:cytology; D019108:Tight Junctions / Q000378:metabolism*; D062827:Zonula Occludens-2 Protein
chemical_list: D015703:Antigens, CD; D000954:Antigens, Surface; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D015415:Biomarkers; D039481:CD11b Antigen; C498497:Cd207 protein, mouse; C498919:Cd274 protein, mouse; D062445:Claudin-1; D057167:Claudins; C568113:Cldn1 protein, mouse; C507360:Cldn7 protein, mouse; D039001:Integrin alpha Chains; D039641:Integrin beta Chains; D037102:Lectins; D037181:Lectins, C-Type; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D010455:Peptides; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C569047:Tjp2 protein, mouse; D062827:Zonula Occludens-2 Protein; C091367:alpha E integrins; C091368:integrin beta7; D018664:Interleukin-12