Transient Receptor Potential Ankyrin1 channel is endogenously expressed in T cells and regulates immune functions

Abstract

Transient Receptor Potential channel subfamily A member 1 (TRPA1) is a non selective cationic channel, identified initially as a cold sensory receptor. TRPA1 responds to diverse exogenous and endogenous stimuli associated with pain and inflammation. However, the role of TRPA1 towards T cell responses remains scanty. In this work, we explored the endogenous expression of TRPA1 in T cells. By RT-PCR we confirmed the expression of TRPA1 in T cell at RNA level. Using confocal microscopy as well as flow cytometry, we demonstrated that TRPA1 is endogenously expressed in primary murine splenic T cells as well as in primary human T cells. The endogenous expression of TRPA1 is confirmed by using another antibody. TRPA1 was primarily located at the cell surface.TRPA1-specific activator namely AITC increases intracellular Ca 2+ -levels while two different inhibitors namely A-967079 as well as HC-030031 reduce intracellular Ca 2+ -levels in T cells. Such Ca 2+ -influx can also be influenced by chelation of intracellular Ca 2+ as well as extracellular Ca 2+ .TRPA1 expression was found to be increased during αCD3/αCD28 (TCR) or ConA driven stimulation in T cells. TRPA1-specific inhibitor treatment prevented induction of CD25, CD69 in ConA/TCR stimulated T cells and secretion of cytokines like TNF, IFN- and IL-2 suggesting that endogenous activity of TRPA1 may be involved in T cell activation. Collectively these results may have implication in T cell-mediated responses and possible role of TRPA1 in immunological disorders.

TRPM8 channel augments T‐cell activation and proliferation

“…Besides regulating intracellular Ca 2+ levels, few TRP channels belonging to the vanilloid (TRPV), melastatin (TRPM), and ankyrin (TRPA1) are also thermosensitive in nature (Baez‐Nieto et al, 2011). Recently, we have shown that heat sensitive TRPA1 channel is functionally present in CD3 + T cells and influences T‐cell activation (Sahoo et al, 2019). We have also shown that the thermosensitive TRPV channels (TRPV1, TRPV2, TRPV3, and TRPV4) are functionally expressed in primary murine and human T cells (Majhi, Sahoo et al, 2015).…”