Authors:
Samuel Bertin, Yukari Aoki-Nonaka, Petrus Rudolf de Jong, Lilian L Nohara, Hongjian Xu, Shawna R Stanwood, Sonal Srikanth, Jihyung Lee, Keith To, Lior Abramson, Timothy Yu, Tiffany Han, Ranim Touma, Xiangli Li, José M González-Navajas, Scott Herdman, Maripat Corr, Guo Fu, Hui Dong, Yousang Gwack, Alessandra Franco, Wilfred A Jefferies, & Eyal Raz
Summary:
TRPV1 is a Ca2+-permeable channel studied mostly as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here we found that TRPV1 was functionally expressed in CD4+ T cells, where it acted as a non–store-operated Ca2+ channel and contributed to T cell antigen receptor (TCR)-induced Ca2+ influx, TCR signaling and T cell activation. In models of T cell–mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4+ T cells recapitulated the phenotype of mouse Trpv1−/− CD4+ T cells. Our findings suggest that inhibition of TRPV1 could represent a new therapeutic strategy for restraining proinflammatory T cell responses.
Source:
Nature Immunology; 15, 1055-1063 (10/05/14)