Abnormal purine metabolism in nasal epithelial cells affects allergic rhinitis by regulating Th17/Treg cells

We aimed to explore novel pathogenesis in young AR children, and thus finding novel nasal spray reagents for them, especially under 4 years old. In this study, non-targeted metabolomics analyses were employed to explore the differential metabolites in NALF of AR children. CCK-8 and flow cytometry were employed to assess cell proliferation and apoptosis in HNEpCs. HNEpCs were co-cultured with CD4 + T cells, and flow cytometry was employed to detect Th17/Treg cells. RNA sequencing was employed to assess the key pathways in xanthine-treated Jurkat T cells. Finally, both the in vitro and in vivo experiments were employed to assess the effect of DPCPX (Adora1 inhibitor) on ATF4 expression and Th17/Treg cells. Xanthine and uric acid levels were increased in NALF of AR children. XDH, PNP, xanthine/hypoxanthine, and uric acid levels were elevated in Derp1-treated HNEpCs, and si-XDH reversed the reduced cell viability and increased cell apoptosis in Derp1-treated HNEpCs. Both xanthine and Derp1-treated HNEpCs increased Th17/Treg ratio. ERS pathway was affected in xanthine-treated Jurkat T cells, and ATF4 was markedly reduced in xanthine-treated Jurkat T cells. Xanthine exhibited no effect on Adora1 expression, while DPCPX elevated ATF4 expression and reduced Th17/Treg ratio in xanthine-treated Jurkat T cells. The in vitro experiments revealed that DPCPX reduced inflammatory infiltration, Th17/Treg ratio, IL-17, TNF-α, and IL-6 in AR mice. These results demonstrated that xanthine inhibited ATF4 expression via Adora1 to elevate Th17/Treg ratio in nasal cavity, thus participating in AR progression. These findings may provide novel therapeutic interventions for young AR children.