The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells
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, 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
Abstract
TRPV1 is a Ca(2+)-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 Ca(2+) channel and contributed to T cell antigen receptor (TCR)-induced Ca(2+) 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.
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Source: PubMed