TRPM8 channel augments T‐cell activation and proliferation

Abstract The transient receptor potential melastatin 8 (TRPM8) is an ion channel that has been widely studied as a cold‐sensitive nociceptor. However, its importance in nonneuronal cells is mostly unexplored. Here, we describe the presence and functional significance of endogenous TRPM8, a nonselective Ca 2+ ‐channel in T cell functions. The major pool of TRPM8 resides at the T cell surface and its surface accumulation significantly increases in activated T cells. TRPM8 activation synergizes with T‐cell receptor (TCR) stimulation to increase CD25, CD69 levels and enhances secretion of proinflammatory cytokine tumor necrosis factor. However, TRPM8 inhibition does not restrict TCR stimulation mediated activation of T cells, indicating that unlike the heat‐sensitive TRPV1 and TRPV4 channels, the cold‐sensitive TRPM8 channel may be dispensable during T‐cell activation, at least in mice. In this study, we demonstrate that TRPM8 promotes TCR‐induced intracellular calcium increase. TRPM8 activation is beneficial for T‐cell activation and differentiation into effector cells. TRPM8 inhibition during the T‐cell activation process may lead to altered phenotype and reduced proliferation, without affecting cell viability. These results collectively establish TRPM8 as a functional calcium channel whose activation may be utilized for mounting an effective immune response. The findings of this study will be relevant to the regulation and response of T cells during cell‐mediated immunity. These results will likely further our understanding on the role of ion channels in T‐cell activation.