Elevation of TRPV1 expression on T cells during experimental immunosuppression

Abstract

An intracellular rise in calcium (Ca2+) is an essential requisite underlying T cell activation and its associated pro-inflammatory cytokine production. Transient receptor potential vanilloid channel (TRPV1) is a thermo-sensitive, polymodal gated and permeable to cations such as Ca2+. It has been reported that TRPV1 expression increases during T cell activation. However, the possible involvement of TRPV1 during immunosuppression of T cells has not been studied yet. Here, we investigated the possible role of TRPV1 in FK506 or B16F10-culture supernatant (B16F10-CS) driven experimental immunosuppression in T cells. Intriguingly, it was found that TRPV1 expression is further elevated during immunosuppression compared to ConA or TCR activated T cells. Similarly, in B16F10 tumor-bearing mice, the TRPV1 expression was upregulated in T cells as compared to control mice, in vivo. Moreover, we observed an immediate rise in intracellular Ca2+ levels in FK506 and B16F10-CS treated T cells as compared to ConA or TCR treated T cells. Likewise, in B16F10 tumor-bearing mice, the basal intracellular calcium level was upregulated in T cells as compared to control mice, in vivo. To further investigate the possible mechanism of such rise in intracellular Ca2+ levels, TRPV1 specific functional inhibitor, 5 -iodoresiniferatoxin (5 -IRTX) was used in calcium influx studies. It was observed that the total intracellular Ca2+ levels decreased significantly in presence of 5 -IRTX for either the FK506 or B16F10-CS as well as with ConA or TCR stimulated T cells, indicating the functional role of TRPV1 channels in FK506 or B16F10-CS mediated increase in intracellular Ca2+ levels. The current findings highlight an essential role of the TRPV1 channel in upregulating intracellular calcium levels during both immune-activation and immunosuppression. This study might also have broad implications in the context of other immune-suppressive diseases as well.