TRPV1 expression and function in splenic dendritic cells: a potential role in immune homeostasis

Neuro-immune interactions, particularly those driven by neuropeptides, are increasingly implicated in immune responses. For instance triggering calcium channel Transient Receptor Potential Vanilloid 1 (TRPV1) on sensory nerves induces the release of CGRP (calcitonin gene related peptide), a neuropeptide known to moderate dendritic cell activation and TH1 polarisation. Despite observations that CGRP is not confined to the nervous system, few studies have addressed the possibility that immune cells can respond to well documented ‘neural’ ligands independently of peripheral nerves. Here we have identified functionally relevant TRPV1 on primary antigen presenting cells of the spleen and have demonstrated both calcium influx and CGRP release in three separate strains of mice using natural agonists. Furthermore, we have shown downregulation of activation markers CD80/86 on dendritic cells, and upregulation of IL6 and IL10 in response to CGRP treatment. We suggest that dendritic cell responses to neural ligands can amplify neuropeptide release, but more importantly that variability in CGRP release across individuals may have important implications for immune cell homeostasis.