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Nat Immunol. 2014 Nov;15(11):1055-1063. doi: 10.1038/ni.3009. Epub 2014 Oct 5.

The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.

Author information

1
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
2
Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, 5274 Gakkocho 2-ban-cho, Chuo-ku, Niigata 951-8514, Japan.
3
Michael Smith Laboratories; Centre for Blood Research; The Brain Research Centre; Department of Medical Genetics; Department of Microbiology and Immunology; Department of Zoology, University of British Columbia, Vancouver, BC, Canada.
4
Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
5
Department of Pediatrics University of California, San Diego, La Jolla, CA 92093, USA.
6
Department of Immunology and Microbial Science, IMM1, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
7
State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
#
Contributed equally

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.

PMID:
25282159
PMCID:
PMC4843825
DOI:
10.1038/ni.3009
[Indexed for MEDLINE]
Free PMC Article

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