TRPA1 ion channel is functionally expressed in CD4 positive T cells and reduces T cell mediated colitis via inhibition of TRPV1
- Author(s): Kim, Peter
- Advisor(s): Raz, Eyal;
- Lu, Li-fan
- et al.
Inflammatory Bowel Diseases (IBD) are characterized by an abnormal inflammation in the small intestine and colon and are mainly mediated by CD4+ T cells. This is why the primary strategy for treating IBD is by therapeutically targeting select CD4+ T cells. It is previously known that the Transient Receptor Potential Vanilloid-1 (TRPV1) ion channel is expressed in CD4+ T cells and functions to activate the proinflammatory characteristics. Furthermore, previous studies show that TRPV1 and TRP Ankyrin 1 (TRPA1) channels in sensory neurons interact with one another in order to affect the level of activity or function of each ion channel. Here, we investigate the possible role of TRPA1 ion channel in CD4+ T cell mediated colitis. First, we show that the TRPA1 channel is infact expressed at the plasma membrane of CD4+ T cells. In addition, Trpa1 gene deletion significantly intensified the T cell mediated colitis in murine models. We also found that TRPA1 inhibits TRPV1 channel which leads to a decrease in CD4+ T cell activation as well as colitogenic characteristics. In IBD patients, TRPA1+TRPV1+ T cell infiltration is significantly increased in the human colonic biopsies.