title: Effect of Polarization on Airway Epithelial Conditioning of Monocyte-Derived Dendritic Cells.
abstract: Airway epithelial cells (AECs) form polarized barriers that interact with inhaled allergens and are involved in immune homeostasis. We examined how monocyte-derived dendritic cells (MDDCs) are affected by contact with the airway epithelium. In traditional setups, bronchial epithelial cell lines were allowed to polarize on filter inserts, and MDDCs were allowed to adhere to the epithelial basal side. In an optimized setup, the cell application was reversed, and the culture conditions were modified to preserve cellular polarization and integrity. These two parameters were crucial for the MDDCs' immunoregulatory properties; thus, previous observations obtained using traditional setups should be considered with caution. Using the optimized setup, AEC conditioning of MDDCs led to increased expression of programmed death 1 ligand 1, immunoglobulin-like transcript 3, CD40, CD80, and CD23. This increased expression was accompanied by decreased secretion of monocyte chemotactic protein 1 and eotaxin and donor-variable effects on IL-12 and IL-10 secretion. Conditioning varied between maturation states and depended partly on direct contact between AECs and MDDCs. The setup allowed MDDCs on the basal side of the epithelium to sample allergens administered to the apical side. Allergen uptake depended on polarization and the nature of the allergen. AEC conditioning led to decreased birch allergen-specific proliferation of autologous T cells and a trend toward decreased secretion of the Th2-specific cytokines IL-5 and IL-13. In conclusion, we determined that AEC conditioning favoring cellular integrity leads to a tolerogenic MDDC phenotype, which is likely to be important in regulating immune responses against commonly inhaled allergens.
authors.affiliation: 1 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.|2 Global Research, ALK, Hoersholm.
authors.forename: Dick
authors.initials: D
authors.lastname: Papazian
authors.affiliation: 1 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
authors.forename: Tashi
authors.initials: T
authors.lastname: Chhoden
authors.affiliation: 1 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
authors.forename: Maria
authors.initials: M
authors.lastname: Arge
authors.affiliation: 3 Biophysical Immunology Laboratory, Department of Biomedicine, Aarhus University, Aarhus; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vorup-Jensen
authors.affiliation: 4 Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
authors.affiliation: 2 Global Research, ALK, Hoersholm.
authors.forename: Kaare
authors.initials: K
authors.lastname: Lund
authors.affiliation: 2 Global Research, ALK, Hoersholm.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Würtzen
authors.affiliation: 1 Department of Cancer and Inflammation Research, Institute of Molecular Medicine, University of Southern Denmark, Odense.
authors.forename: Soren
authors.initials: S
authors.lastname: Hansen
mesh_terms: D000485:Allergens / Q000276:immunology; D029662:Betula / Q000276:immunology; D002460:Cell Line; D016764:Cell Polarity; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D031784:Phleum / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D000485:Allergens
keywords: allergy; epithelial polarization; immune regulation; tolerance