Th76 - The Effect of TRPV1+ Neuron-derived Neuropeptides on Cytokine Production of Th1 and Th17 Cells

In periodontitis, Th1 and Th17 cells in inflammatory sites mediate host defense against bacterial infection but are also involved in tissue destruction. TRPV1⁺ neurons that sense noxious stimulus are densely innervated in oral mucosa and secrete substance P, CGRP and glutamate in inflammatory conditions. Recent studies have shown that calcitonin gene-related peptide (CGRP) promotes Th17 differentiation and Th17 cell functions. However, the effect of neuropeptides on Th1 cells has not been studied yet. In this study, we investigated the effects of neuropeptides on cytokine production in Th1 and Th17 cells. Th1 and Th17 cells were differentiated by in vitro culture of isolated CD4⁺ T cells from C57BL/6 mice with polarizing cytokines in RPMI medium. Both Th1 and Th17 cells expressed CGRP receptor genes (receptor-activity-modifying protein 1 and calcitonin-like receptor) and a glutamate receptor gene Grina but no substance P receptor genes. In addition, calcium influx in response to CGRP and N-methyl-D-aspartate (NMDA), a glutamate receptor agonist, was confirmed in Th17 cells. To examine the effect of neuropeptides on cytokines production in T cells, TCR- or bystander-activated Th1 and Th17 cells were stimulated with either CGRP or NMDA. CGRP did not affect IFNγ production in Th1 cells and decreased TCR-activated IL-17 production (0.9 fold) but increased bystander-activated IL-17 production (4.8 fold) in Th17 cells. NMDA increased TCR-activated IFNγ production (1.5 fold) in Th1 cells and TCR-activated IL-17 production (1.3 fold) in Th17 cells. Taken together, TRPV1⁺ neuron-derived CGRP and NMDA increased the function of both Th1 and Th17 cells in vitro.