Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice

Abstract

© 2016 the American Physiological Society. Givi ME, Akbari P, Boon L, Puzovic VS, Bezemer GF, Ricciardolo FL, Folkerts G, Redegeld FA, Mortaz E. Dendritic cells inversely regulate airway inflammation in cigarette smoke-exposed mice. Am J Physiol Lung Cell Mol Physiol 310: L95-L102, 2016. First published October 16, 2015; doi:10.1152/ajplung.00251.2014.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. CSexposed 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 compartmentdependent 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.