biostudies-literatureUnknown14(10)Yin LPurinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y₆R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y₆R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y₆R and Th1 cells mediated by IL-27. Mechanistically, P2Y₆R enhanced PLC _<i>β</i> /p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, leadActa pharmaceutica Sinica. B4360-4377https://www.ebi.ac.uk/biostudies/studies/S-EPMC11544167biostudies-literatureMacrophage P2Y&lt;sub&gt;6&lt;/sub&gt;R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses.PMC11544167Zhou MLi HZhang ENi KMao TZhu YLu YNi SFang YLi YLiu CHu QYin LfalseMacrophage P2Y&lt;sub&gt;6&lt;/sub&gt;R activation aggravates psoriatic inflammation through IL-27-mediated Th1 responses.Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y₆R mainly distributed in macrophages was significantly up-expressed in skin lesions from patients with psoriasis in the present study. Here, the severity of psoriasis was alleviated in imiquimod-treated mice with macrophages conditional knockout of P2Y₆R, while the cell-chat algorithm showed there was a correlation between macrophage P2Y₆R and Th1 cells mediated by IL-27. Mechanistically, P2Y₆R enhanced PLC _<i>β</i> /p-PKC/MAPK activation to induce IL-27 release dependently, which subsequently regulated the differentiation of Th1 cells, lead2024-01-01T00:00:00Z2024 Oct2025-04-22T16:25:05.127Z2025-04-06T01:45:20.727ZS-EPMC115441673952558710.1016/j.apsb.2024.06.008