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 Ca²⁺‐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.

中文翻译：

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TRPM8 通道增强 T 细胞活化和增殖

瞬时受体电位 melastatin 8 (TRPM8) 是一种离子通道，已被广泛研究为冷敏感伤害感受器。然而，它在非神经元细胞中的重要性大多未被探索。在这里，我们描述了内源性 TRPM8（一种非选择性 Ca ^2+）的存在和功能意义-T 细胞功能中的通道。TRPM8 的主要池位于 T 细胞表面，其表面积累在活化的 T 细胞中显着增加。TRPM8 激活与 T 细胞受体 (TCR) 刺激协同增加 CD25、CD69 水平并增强促炎细胞因子肿瘤坏死因子的分泌。然而，TRPM8 抑制并不限制 TCR 刺激介导的 T 细胞激活，这表明与热敏性 TRPV1 和 TRPV4 通道不同，冷敏性 TRPM8 通道在 T 细胞激活期间可能是可有可无的，至少在小鼠中是这样。在这项研究中，我们证明 TRPM8 促进 TCR 诱导的细胞内钙增加。TRPM8 激活有利于 T 细胞激活和分化为效应细胞。在 T 细胞活化过程中抑制 TRPM8 可能导致表型改变和增殖减少，而不影响细胞活力。这些结果共同将 TRPM8 确立为功能性钙通道，其激活可用于启动有效的免疫反应。这项研究的结果将与细胞介导的免疫过程中 T 细胞的调节和反应有关。这些结果可能会进一步加深我们对离子通道在 T 细胞活化中的作用的理解。