sb-366791 and Colitis

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.

Topics: Anilides; Animals; Calcium; Calcium Channels; Calcium Signaling; Capsaicin; CD4-Positive T-Lymphocytes; Cells, Cultured; Cinnamates; Colitis; Humans; Inflammation; Interleukin-10; Intestines; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Antigen, T-Cell; Sensory System Agents; TRPV Cation Channels