NK1R- and NK2R-dependent neuropeptide signaling regulates Type-1 immunity through activation of dendritic cells (INC6P.336)

Abstract

Abstract Neurotransmitters such as Substance P (SP) and Neurokinin A (NKA) are widely distributed in both central and peripheral nervous system. Recently, we demonstrated that IFN-γ remarkably induced neurokinin-2 receptor (NK2R) expression in human dendritic cells (DCs). These findings strongly suggested that neuropeptide-signaling might regulate function of human DCs DC-mediated immune responses. In this study, we examined the effect of neuropeptide signaling on DC function. Human DCs generated from peripheral blood mononuclear cells (PBMCs) were treated with various type I cytokines or toll-like receptor ligands. Both neurokinin-1 receptor (NK1R) and NK2R mRNA expressions in DCs were significantly enhanced by poly I:C stimulation. The upregulation of NK1R and NK2R mRNA expressions was blocked in the presence of STAT-1 inhibitor. Surface expression levels of HLA-DR and costimulatory molecules on DCs, augmented by poly I:C, were modulated by NK1R or NK2R inhibitor. In addition, we found that blockade of NK1R- and NK2R-mediated signaling significantly suppressed various cytokine productions by antigen-specific CD4+ T cells stimulated with DCs. These findings indicate that NK1R- and NK2R-dependent neuropeptide signaling regulate Type-1 immunity through the activation of DCs, suggesting that such neuro-immune cross-talk through NK1R and NK2R signaling might be involved in various diseases with chronic inflammation caused by excessive Type-1-dominant immunity.