The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4+ T cells
Nat Immunol. 2014 Oct 5. doi: 10.1038/ni.3009.
Samuel Bertin1, Yukari Aoki-Nonaka1,2, Petrus Rudolf de Jong1, Lilian L Nohara3,8, Hongjian Xu3,8, Shawna R Stanwood3, Sonal Srikanth4, Jihyung Lee1, Keith To1, Lior Abramson1, Timothy Yu1, Tiffany Han1, Ranim Touma5, Xiangli Li1, José M González-Navajas1, Scott Herdman1, Maripat Corr1, Guo Fu6,7, Hui Dong1, Yousang Gwack4, Alessandra Franco5, Wilfred A Jefferies3 & Eyal Raz1
1Department of Medicine, University of California, San Diego, La Jolla, California, USA. 2Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. 3Michael Smith Laboratories, Centre for Blood Research, The Brain Research Centre, Department of Medical Genetics, Department of Microbiology and Immunology and Department of Zoology, University of British Columbia, Vancouver, Canada. 4Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA. 5Department of Pediatrics University of California, San Diego, La Jolla, California, USA. 6Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA. 7State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Fujian, China. 8These authors contributed equally to this work. Correspondence should be addressed to W.A.J. (email@example.com) or E.R. (firstname.lastname@example.org).
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.