258-LB: Vitamin D Directly Regulates TRPV1 Channel Activity and May Play an Important Role in the Autoimmune Disease of Type 1 Diabetes

The autoimmune disease of type 1 diabetes (T1D) results in the immune destruction of β-cells. Recent studies suggest supplementation of vitamin D along can significantly improve patients’ β-cell function and glycemic control possibly by dampening naive T-cell activation. However, the underlying cellular mechanism for this effect has not been elucidated completely, especially as naive T-cells possess absent or very low VDR expression. Therefore, the effects of Vitamin D on naive T-cells may involve a VDR-independent pathway. Interestingly, TRPV1 channel activation is necessary for naive T-cell activation. Our initial calcium imaging and electrophysiological data show that Vitamin D (25OHD) can partially activate TRPV1. 25OHD can inhibit capsaicin induced TRPV1 activity. We propose that vitamin D is a partial agonist of TRPV1, through direct binding to TRPV1 and modulating naive T-cell activation. Furthermore, our flow cytometry studies confirm both 25OHD and 1,25OHD significantly reduce TNFα/INFγ and IL2/IL4 production of mouse CD4+ naive T-cells after 24 hours activation. Our results support the concept that naive T-cell activation can be dampened by vitamin D in a VDR-independent manner, via an as yet undescribed mechanism involving the modulation of TRPV1 activity. Moreover, in silico and point-muatgenic experiments indicate 25-OHD binds to the same region as known TRPV1 agonist and antagonists. These novel findings provide evidence of an additional pathway for the action of Vitamin D action and advance our knowledge of the underlying cellular mechanism by which vitamin D may beneficially regulate naive T-cell activation in autoimmune disease such as T1D. Disclosure W. Long: Research Support; Self; JDRF. M. Fatehi: None. S. Soni: None. R. Panigrahi: None. R.G. Kelly: None. K. Philippaert: None. A.J. Barr: None. M. Held: None. Y. Yu: None. S.A. Campbell: None. K. Ondrusova: None. T. Baldwin: None. J. Lemieux: None. P.E. Light: None. Funding JDRF