National Institute for Health, Migration and Poverty INMP/NIHMP, Via di S.Gallicano, 25, 00153 Rome, Italy.
National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Via Portuense 292, 00149 Rome, Italy.
Int J Mol Sci. 2023 Sep 29;24(19):14736. doi: 10.3390/ijms241914736.
Transient receptor potential ankyrin 1 (TRPA1) channels are expressed on the surface of different cell types, including immune cells. However, TRPA1's role in the context of innate and adaptive immune responses has not been fully elucidated so far. In this study, we aimed at investigating the expression and function of TRPA1 channels on NK cells. Among NK cells, TRPA1 was highly expressed by the CD56CD16 subpopulation, but not by CD56CD16 cells, as detected by FACS. TRPA1 activation with the potent ligand allyl isothiocyanate (AITC) induces intracellular calcium flux in CD56CD16 cells, which was prevented by the TRPA1 antagonist HC-030031. AITC treatment increased the membrane around NKp44 and strongly decreased CD16 and CD8 expression, while CD158a, CD159a, NKG2d, NKp46 were substantially unaffected. Importantly, AITC increased the granzyme production and CD107 expression and increased NK cell-mediated cytotoxicity towards the K562 cell line and two different melanoma cell lines. In parallel, TRPA1 activation also plays regulatory roles by affecting the survival of NK cells to limit uncontrolled and prolonged NK cell-mediated cytotoxicity. Our results indicate that the activation of TRPA1 is an important regulatory signal for NK cells, and agonists of TRPA1 could be used to strengthen the tumor response of the immune system.
瞬时受体电位锚蛋白 1（TRPA1）通道表达于不同细胞类型的表面，包括免疫细胞。然而，TRPA1 在先天和适应性免疫反应中的作用迄今尚未完全阐明。在这项研究中，我们旨在研究 NK 细胞上 TRPA1 通道的表达和功能。通过流式细胞术检测到，在 NK 细胞中，TRPA1 高度表达于 CD56CD16 亚群，但不表达于 CD56CD16 细胞。TRPA1 激动剂丙烯基异硫氰酸酯（AITC）的激活可诱导 CD56CD16 细胞内钙离子流，该作用可被 TRPA1 拮抗剂 HC-030031 阻断。AITC 处理增加了 NKp44 周围的膜，并强烈降低了 CD16 和 CD8 的表达，而 CD158a、CD159a、NKG2d、NKp46 则基本不受影响。重要的是，AITC 增加了颗粒酶的产生和 CD107 的表达，并增加了 NK 细胞对 K562 细胞系和两种不同黑素瘤细胞系的细胞毒性。与此同时，TRPA1 的激活也通过影响 NK 细胞的存活来发挥调节作用，以限制不受控制和延长的 NK 细胞介导的细胞毒性。我们的结果表明，TRPA1 的激活是 NK 细胞的一个重要调节信号，TRPA1 的激动剂可用于增强免疫系统对肿瘤的反应。
