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Phasic regulation of the ATP/P2X7 receptor signaling pathway affects the function of antigen-presenting cells in experimental autoimmune uveitis

Peng, X;Zhang, Y;Bai, X;Li, X;Zhao, R;

Purinergic ligand-gated ion channel 7 receptor (P2X7R) is a purine type P2 receptor that is expressed on a variety of immune cells. Recent studies have shown that P2X7R signaling is required to trigger an immune response, and P2X7R antagonist-oxidized ATP (oxATP) effectively blocks P2X7R activation. In this study, we investigated the effect of phasic regulation of the ATP/P2X7R signaling pathway on antigen-presenting cells (APCs) by constructing an experimental autoimmune uveitis (EAU) disease model. Our results demonstrated that APCs isolated from the 1st, 4th, 7th and 11th days of EAU presented antigen function and could stimulate the differentiation of naive T cells. Moreover, after stimulation by ATP and BzATP (a P2X7R agonist), antigen presentation, promoting differentiation and inflammation were enhanced. The regulation of the Th17 cell response was significantly stronger than that of the Th1 cell response. In addition, we verified that oxATP blocked the P2X7R signaling pathway on APCs, attenuated the effect of BzATP, and significantly improved the adoptive transfer EAU induced by antigen-specific T cells cocultured with APCs. Our results demonstrated that at an early stage of EAU, the ATP/P2X7R signaling pathway regulation of APCs was time dependent, and the treatment of EAU could be achieved by intervening in P2X7R function on APCs.