title: The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.
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.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Bertin
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.|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.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Aoki-Nonaka
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Petrus Rudolf
authors.initials: PR
authors.lastname: de Jong
authors.affiliation: 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.
authors.forename: Lilian L
authors.initials: LL
authors.lastname: Nohara
authors.affiliation: 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.
authors.forename: Hongjian
authors.initials: H
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Shawna R
authors.initials: SR
authors.lastname: Stanwood
authors.affiliation: Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Sonal
authors.initials: S
authors.lastname: Srikanth
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Jihyung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: To
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lior
authors.initials: L
authors.lastname: Abramson
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Han
authors.affiliation: Department of Pediatrics University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Ranim
authors.initials: R
authors.lastname: Touma
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: José M
authors.initials: JM
authors.lastname: González-Navajas
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Herdman
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Maripat
authors.initials: M
authors.lastname: Corr
authors.affiliation: Department of Immunology and Microbial Science, IMM1, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.|State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Fujian 361102, China.
authors.forename: Guo
authors.initials: G
authors.lastname: Fu
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Physiology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yousang
authors.initials: Y
authors.lastname: Gwack
authors.affiliation: Department of Pediatrics University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Franco
authors.affiliation: 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.
authors.forename: Wilfred A
authors.initials: WA
authors.lastname: Jefferies
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Eyal
authors.initials: E
authors.lastname: Raz
mesh_terms: D000813:Anilides / Q000494:pharmacology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000276:immunology; D020013:Calcium Signaling / Q000187:drug effects / Q000276:immunology; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology; D003092:Colitis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D016753:Interleukin-10 / Q000235:genetics; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D018689:Sensory System Agents / Q000494:pharmacology; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D000813:Anilides; D015220:Calcium Channels; D002934:Cinnamates; C556062:IL10 protein, mouse; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D011948:Receptors, Antigen, T-Cell; D018689:Sensory System Agents; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D016753:Interleukin-10; D002211:Capsaicin; D002118:Calcium