title: Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice.
abstract: The recruitment and activation of inflammatory cells into the respiratory system is considered a crucial feature in the pathophysiology of chronic obstructive pulmonary disease (COPD). Because dendritic cells (DCs) have a pivotal role in the onset and regulation of immune responses, we investigated the effect of modulating DC subsets on airway inflammation by acute cigarette smoke (CS) exposure. CS-exposed mice (5 days) were treated with fms-like tyrosine kinase 3 ligand (Flt3L) and 120g8 antibody to increase total DC numbers and deplete plasmacytoid DCs (pDCs), respectively. Flt3L treatment decreased the number of inflammatory cells in the bronchoalveolar lavage (BALF) of the smoke-exposed mice and increased these in lung tissue. DC modulation reduced IL-17 and increased IL-10 levels, which may be responsible for the suppression of the BALF cells. Furthermore, depletion of pDCs led to increased infiltration of alveolar macrophages while restricting the presence of CD103(+) DCs. This study suggests that DC subsets may differentially and compartment-dependent influence the inflammation induced by CS. pDC may play a role in preventing the pathogenesis of CS by inhibiting the alveolar macrophage migration to lung and increasing CD103(+) DCs at inflammatory sites to avoid extensive lung tissue damage.
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Faculty of Veterinary Medicine, Department of Pharmacology and Toxicology, Shahid Chamran University, Ahvaz, Iran;
authors.forename: Masoumeh Ezzati
authors.initials: ME
authors.lastname: Givi
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
authors.forename: Peyman
authors.initials: P
authors.lastname: Akbari
authors.affiliation: Bioceros BV, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.affiliation: Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia;
authors.forename: Vladimir S
authors.initials: VS
authors.lastname: Puzovic
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
authors.forename: Gillina F G
authors.initials: GF
authors.lastname: Bezemer
authors.affiliation: Division of Respiratory Disease, Department of Clinical and Biological Sciences, University of Torino, Orbassano (Torino), Italy; and.
authors.forename: Fabio L M
authors.initials: FL
authors.lastname: Ricciardolo
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands;
authors.forename: Gert
authors.initials: G
authors.lastname: Folkerts
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; f.a.m.redegeld@uu.nl.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Redegeld
authors.affiliation: Faculty of Science, Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Faculty of Medicine, Department of Immunology, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Esmaeil
authors.initials: E
authors.lastname: Mortaz
mesh_terms: D000818:Animals; D001991:Bronchitis / Q000378:metabolism* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D020381:Interleukin-17 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
chemical_list: C508717:IL17A protein, human; D020381:Interleukin-17
keywords: chronic obstructive pulmonary disease