Novel regulation of NFAT activation by TRPV1 in CD⁴⁺ T cells
- Author(s): Quinley, Christine Caitlin
- et al.
TRPV1 is both a receptor and non-selective Ca²⁺ channel. TRPV1 was first described in primary afferent neurons to function as a receptor of noxious stimuli, and is thus integral to pain perception by higher brain areas. Since its initial discovery, TRPV1 has been shown to be expressed in a number of non-neuronal tissues, including cells of the immune system, e.g., T lymphocytes. Our lab demonstrated for the first time that TRPV1 is a functional calcium channel in CD⁴⁺ T cells. We have shown that Ca²⁺ influx via TRPV1 is required for proper activation of T lymphocytes by promoting the activation of TCR-mediated downstream signaling pathways. Of these signaling pathways, NFAT signaling is most dependent on Ca²⁺ for its activation and its transcriptional activity. Since CD⁴⁺ lymphocytes play a major role in regulating and maintaining activation of the adaptive immune system, we chose to explore the specific regulatory role of TRPV1 in these cells by focusing on NFAT signaling. In our study we identify TRPV1 as a key regulator of NFAT signaling both at steady-state and upon TCR ligation. TRPV1 was shown to inhibit the steady-state nuclear translocation of NFAT and to inhibit TCR-mediated NFAT down-regulation, identifying TRPV1 as a potential therapeutic target for regulating T cell activation and the development and progression of T cell-mediated diseases