Majhi Rakesh K, Sahoo Subhransu S, Yadav Manoj, Pratheek Belluru M, Chattopadhyay Subhasis, Goswami Chandan
School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar, Orissa, India.
FEBS J. 2015 Jul;282(14):2661-81. doi: 10.1111/febs.13306. Epub 2015 May 28.
The importance of Ca(2+) signalling and temperature in the context of T cell activation is well known. However, the molecular identities of key players involved in such critical regulations are still unknown. In this work we explored the endogenous expression of transient receptor potential vanilloid (TRPV) channels, a group of thermosensitive and non-selective cation channels, in T cells. Using flow cytometry and confocal microscopy, we demonstrate that members belonging to the TRPV subfamily are expressed endogenously in the human T cell line Jurkat, in primary human T cells and in primary murine splenic T cells. We also demonstrate that TRPV1- and TRPV4-specific agonists, namely resiniferatoxin and 4α-phorbol-12,13-didecanoate, can cause Ca(2+) influx in T cells. Moreover, our results show that expression of these channels can be upregulated in T cells during concanavalin A-driven mitogenic and anti-CD3/CD28 stimulated TCR activation of T cells. By specific blocking of TRPV1 and TRPV4 channels, we found that these TRPV inhibitors may regulate mitogenic and T cell receptor mediated T cell activation and effector cytokine(s) production by suppressing tumour necrosis factor, interleukin-2 and interferon-γ release. These results may have broad implications in the context of cell-mediated immunity, especially T cell responses and their regulations, neuro-immune interactions and molecular understanding of channelopathies.
Ca(2+)信号传导和温度在T细胞活化过程中的重要性是众所周知的。然而，参与此类关键调节的关键分子身份仍然未知。在这项工作中，我们探索了瞬时受体电位香草酸（TRPV）通道的内源性表达，这是一组热敏性和非选择性阳离子通道，存在于T细胞中。使用流式细胞术和共聚焦显微镜，我们证明TRPV亚家族的成员在人T细胞系Jurkat、原代人T细胞和原代小鼠脾T细胞中内源性表达。我们还证明，TRPV1和TRPV4特异性激动剂，即树脂毒素和4α-佛波醇-12,13-二癸酸酯，可导致T细胞中的Ca(2+)内流。此外，我们的结果表明，在伴刀豆球蛋白A驱动的有丝分裂和抗CD3/CD28刺激的T细胞TCR活化过程中，这些通道的表达可在T细胞中上调。通过特异性阻断TRPV1和TRPV4通道，我们发现这些TRPV抑制剂可能通过抑制肿瘤坏死因子、白细胞介素-2和干扰素-γ的释放来调节有丝分裂和T细胞受体介导的T细胞活化以及效应细胞因子的产生。这些结果可能在细胞介导的免疫、特别是T细胞反应及其调节、神经免疫相互作用以及通道病的分子理解方面具有广泛的意义。
