title: Aeroallergen challenge promotes dendritic cell proliferation in the airways.
abstract: Aeroallergen provocation induces the rapid accumulation of CD11c(+)MHC class II (MHC II)(+) dendritic cells (DCs) in the lungs, which is driven by an increased recruitment of blood-derived DC precursors. Recent data show, however, that well-differentiated DCs proliferate in situ in various tissues. This may also contribute to their allergen-induced expansion; therefore, we studied DC proliferation in the airways of mice in the steady state and after local aeroallergen provocation. Confocal whole-mount microscopy was used to visualize proliferating DCs in different microanatomical compartments of the lung. We demonstrate that in the steady state, CD11c(+)MHC II(+) DCs proliferate in both the epithelial and subepithelial layers of the airway mucosa as well as in the lung parenchyma. A 1-h pulse of the nucleotide 5-ethynyl-2'-deoxyuridine was sufficient to label 5% of DCs in both layers of the airway mucosa. On the level of whole-lung tissue, 3-5% of both CD11b(+) and CD11b(-) DC populations and 0.3% of CD11c(+)MHC II(low) lung macrophages incorporated 5-ethynyl-2'-deoxyuridine. Aeroallergen provocation caused a 3-fold increase in the frequency of locally proliferating DCs in the airway mucosa. This increase in mucosal DC proliferation was later followed by an elevation in the number of DCs. The recruitment of monocyte-derived inflammatory DCs contributed to the increasing number of DCs in the lung parenchyma, but not in the airway mucosa. We conclude that local proliferation significantly contributes to airway DC homeostasis in the steady state and that it is the major mechanism underlying the expansion of the mucosal epithelial/subepithelial DC network in allergic inflammation.
authors.affiliation: Department of Airway Immunology, Fraunhofer Institute for Toxicology and Experimental Medicine, 30625 Hannover, Germany.
authors.forename: Tibor Z
authors.initials: TZ
authors.lastname: Veres
authors.forename: Sabrina
authors.initials: S
authors.lastname: Voedisch
authors.forename: Emma
authors.initials: E
authors.lastname: Spies
authors.forename: Joona
authors.initials: J
authors.lastname: Valtonen
authors.forename: Frauke
authors.initials: F
authors.lastname: Prenzler
authors.forename: Armin
authors.initials: A
authors.lastname: Braun
mesh_terms: D019264:Adoptive Transfer; D000336:Aerosols; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001980:Bronchi / Q000276:immunology / Q000473:pathology; D002455:Cell Division; D019070:Cell Lineage; D003433:Crosses, Genetic; D004261:DNA Replication; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D004848:Epithelium / Q000276:immunology / Q000473:pathology; D018928:Immunity, Mucosal; D007114:Immunization; D007249:Inflammation; D008168:Lung / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000276:immunology / Q000637:transplantation; D009092:Mucous Membrane / Q000276:immunology / Q000473:pathology; D009928:Organ Specificity; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D012137:Respiratory System / Q000276:immunology* / Q000473:pathology
chemical_list: D000336:Aerosols; D000485:Allergens; D010047:Ovalbumin; D016186:Receptor, Macrophage Colony-Stimulating Factor