Promoting dendritic cell migration by mouse airway epithelial cells through IL-17A-induced mouse CCL20 expression (40.10)

Abstract

Abstract Dendritic cells are the antigen presenting cells that play a central role in regulating immune response. Their migration on airway epithelium in response to antigen challenge is incompletely understood. In this study, we demonstrated that mouse IL-17A is a potent stimulator for primary mouse airway epithelium to secrete chemotactic factors for the migration of bone marrow-derived dendritic cells (BMDC) along its gradient. Neutralizing antibody study with anti-mCCL20 demonstrated the inhibition of the migration. Real-time quantitative RT-PCR study demonstrated time- and dose-dependent effects of IL-17A on mCCL20 expression, but not the induction of hBD-2 equivalent messages, in mouse airway epithelial cells. The lack of induction of hBD-2 equivalent messages by IL-17A on mouse cell system is in contrast to that was seen in human, suggesting a species difference in response to IL-17A. Using inhibitor, we observed the inhibition of induced CCL20 expression by an NF-κB inhibitor, isohelenin, suggesting an NF-κB mediated transcriptional mechanism in the induction. Based on these observations, we suggest that IL-17A may be responsible for in vivo dendritic cell migration on airway epithelium through the induction of mCCL20 expression. This study is supported by NIH grant HL077315 and HL077902