TRPA1 Covalent Ligand JT010 Modifies T Lymphocyte Activation

oleh: Katalin Szabó, Géza Makkai, János Konkoly, Viktória Kormos, Balázs Gaszner, Tímea Berki, Erika Pintér

Format: Article
Diterbitkan: MDPI AG 2024-05-01

Deskripsi

Transient Receptor Potential Ankyrin 1 (TRPA1) is a non-selective cation channel involved in sensitivity to a plethora of irritating agents and endogenous mediators of oxidative stress. TRPA1 influences neuroinflammation and macrophage and lymphocyte functions, but its role is controversial in immune cells. We reported earlier a detectable, but orders-of-magnitude-lower level of <i>Trpa1</i> mRNA in monocytes and lymphocytes than in sensory neurons by qRT-PCR analyses of cells from lymphoid organs of mice. Our present goals were to (a) further elucidate the expression of <i>Trpa1</i> mRNA in immune cells by RNAscope in situ hybridization (ISH) and (b) test the role of TRPA1 in lymphocyte activation. RNAscope ISH confirmed that <i>Trpa1</i> transcripts were detectable in CD14<sup>+</sup> and CD4<sup>+</sup> cells from the peritoneal cavity of mice. A selective TRPA1 agonist JT010 elevated Ca<sup>2+</sup> levels in these cells only at high concentrations. However, a concentration-dependent inhibitory effect of JT010 was observed on T-cell receptor (TcR)-induced Ca<sup>2+</sup> signals in CD4<sup>+</sup> T lymphocytes, while JT010 neither modified B cell activation nor ionomycin-stimulated Ca<sup>2+</sup> level. Based on our present and past findings, TRPA1 activation negatively modulates T lymphocyte activation, but it does not appear to be a key regulator of TcR-stimulated calcium signaling.