P2X7 Drives T-cell Activation Promoting Chronic Inflammation During High Blood Pressure 9289

Abstract Description Chronic inflammation is often seen in hypertension, potentially worsening infection outcomes. Previously, our group found high blood pressure stimulates T cell activation via ATP-P2X7 signaling. Given the persistent nature of hypertension, we hypothesize that sustained T cell activation and memory formation contribute to the pathogenesis of chronic inflammation. This study used a classic model of hypertension, DOCA-salt mice. T cells isolated from the spleen and blood were analyzed using full-spectrum flow cytometry. Compared to controls, hypertensive mice displayed a larger population of activated CD8Ts characterized by elevated CD44 and increased production of cytokines IFN-γ and TNF-α. Notably, these hypertensive CD44+CD8Ts also exhibited higher CD127 expression, indicating a precursor to memory CD8Ts. Further analysis revealed significant enrichment of Tcm (CD62L+) and Tem (CD62L-) in the hypertensive group relative to controls. Unexpectedly, we also found a greater frequency of Il-17-secreting Tc17 cells (RORγ+Il-17a+) in hypertensive mice. Intriguingly, these expanded Tc17s, Tcms, and Tems exhibited higher P2X7 expression, implying that augmented P2X7 signaling under hypertensive conditions may contribute to forming these long-living, memory-type CD8Ts. We conclude that high blood pressure promotes the differentiation of T cells into memory phenotype via P2X7-dependent signaling. Our ongoing studies are using P2X7-KO mice to validate these findings further. Funding Sources NIH R01-HL146713 AHA 23TPA1076467 Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)