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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Anilides / pharmacology
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Animals
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / immunology*
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Calcium / metabolism
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Calcium Channels / immunology
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Calcium Signaling / drug effects
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Calcium Signaling / immunology
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Capsaicin / pharmacology
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Cells, Cultured
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Cinnamates / pharmacology
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Colitis / immunology
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Humans
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Inflammation / immunology*
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Interleukin-10 / genetics
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Intestines / immunology
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Intestines / pathology
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Lymphocyte Activation / drug effects
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Lymphocyte Activation / immunology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell / metabolism*
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Sensory System Agents / pharmacology
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TRPV Cation Channels / antagonists & inhibitors
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TRPV Cation Channels / biosynthesis
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TRPV Cation Channels / genetics*
Substances
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Anilides
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Calcium Channels
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Cinnamates
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IL10 protein, mouse
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N-(3-methoxyphenyl)-4-chlorocinnamanilide
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Receptors, Antigen, T-Cell
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Sensory System Agents
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TRPV Cation Channels
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TRPV1 protein, mouse
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Interleukin-10
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Capsaicin
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Calcium