BACKGROUND The P2X7 ion channel, a key sensor of sterile inflammation, has been implicated as a therapeutic target in glomerulonephritis, and P2X7-antagonistic nanobodies can attenuate experimental glomerulonephritis. However, little is known about the expression of P2X7 on renal immune cells. METHODS We used conventional immunofluorescence of kidney sections as well as intraperitoneal injection of nanobodies in mice followed by flow cytometry analysis of parenchymal T cells and RNA-sequencing to elucidate the expression and function of P2X7 on parenchymal and vascular immune cells in the mouse kidney. RESULTS Our study showed that parenchymal T cells, including a large subset of natural killer T cells and CD69+ tissue-resident memory T cells, display much higher cell surface levels of P2X7 than vascular T cells. After a single intraperitoneal injection of P2X7-blocking nanobodies, P2X7 on parenchymal T cells was fully occupied by the injected nanobodies within 30 min. This resulted in an effective protection of these cells from NAD-induced cell death during cell preparation. Conversely, systemic injection of NAD that mimics sterile inflammation results in the selective depletion of P2X7hiCD69hi T cells from the kidney parenchyma. CONCLUSIONS Our study uncovered a novel purinergic regulatory mechanism affecting kidney-resident T cell populations.

中文翻译：

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肾内炎症中肾脏驻留自然杀伤 T 细胞和记忆 T 细胞上的 ATP 门控 P2X7 离子通道。


背景 P2X7 离子通道是无菌性炎症的关键传感器，被认为是肾小球肾炎的治疗靶点，P2X7 拮抗纳米抗体可以减轻实验性肾小球肾炎。然而，人们对 P2X7 在肾免疫细胞上的表达知之甚少。方法 我们使用肾脏切片的常规免疫荧光以及小鼠腹腔注射纳米抗体，然后对实质 T 细胞进行流式细胞术分析和 RNA 测序，以阐明 P2X7 在小鼠肾脏实质和血管免疫细胞上的表达和功能。结果我们的研究表明，实质 T 细胞，包括一大群自然杀伤 T 细胞和 CD69+ 组织驻留记忆 T 细胞，显示出比血管 T 细胞高得多的 P2X7 细胞表面水平。单次腹膜内注射 P2X7 阻断纳米抗体后，实质 T 细胞上的 P2X7 在 30 分钟内被注射的纳米抗体完全占据。这导致这些细胞在细胞制备过程中免受 NAD 诱导的细胞死亡。相反，模拟无菌性炎症的全身注射 NAD 导致肾实质中 P2X7hiCD69hi T 细胞的选择性耗竭。结论 我们的研究发现了一种影响肾脏驻留 T 细胞群的新型嘌呤能调节机制。