Oxidative stress-induced pulmonary neutrophil recruitment is independent of conventional dendritic cells (INC5P.325)

Abstract

Abstract Oxidative stress and airway neutrophilia are key features of some asthma phenotypes. Ozone (O3), a potent oxidant, induces pulmonary neutrophil recruitment which requires IL-17A+ γδ T cells. IL-23 is required for IL-17A production by T cells and conventional dendritic cells (cDC) are a potent source of IL-23. We therefore hypothesized that oxidative stress-induced IL-17A+ γδ T cells require IL-23 production from cDC. Wild type (WT), Tcrd-/- (lacking γδ T cells), and flt3l-/- (deficient in cDC) mice were exposed to air or 0.3 ppm O3 for 72 h. Bronchoalveolar lavage (BAL) was collected for cell differentials and lungs were processed for qPCR analysis. Lungs from mice which were not lavaged were used for flow cytometric analysis. In WT mice, O3 caused a 4 fold increase in the percentage of lung CD11c+/MHCII+/Siglec-F+ dendritic cells. IL-23 mRNA was also increased after O3 exposure. Flt3l-/- and WT mice had similar amounts of IL-23 and IL-17A mRNA and BAL neutrophils, thus indicating that cDC are not the source of IL-23 after such oxidative stress. However, IL-23 mRNA was reduced in Tcrd-/- mice which had fewer CD11c-/ CD11b+/F4/80+ myeloid cells. These cells are thus the potential source of IL-23. Altogether these data suggest oxidative stress induces IL-23 production by non-dendritic myeloid cells leading to IL-17A+ γδ T cell driven neutrophil recruitment.