Rvd1 Alleviates Periodontitis By Promoting M2 Macrophage Polarization And Efferocytosis

This study investigates the therapeutic effects of Resolvin D1 (RvD1) in periodontitis, focusing on its role in macrophage polarization, efferocytosis, and inflammation resolution via the Fpr2 receptor. Periodontitis was induced in wild-type and Fpr2Lyz2-cKO mice, divided into control (N/NcKO), disease (L/LcKO), and RvD1-treated (R/RcKO) groups. The Fpr2 receptor’s role was evaluated by conditional knockout in monocytic cells in vivo. Techniques including single-cell sequencing of alveolar bone cells, immunofluorescence, histopathological staining, immunohistochemistry, and micro-CT for alveolar bone assessment were employed to study RvD1’s effects on macrophage polarization, necroptosis, and efferocytosis. RvD1 reduced periodontal inflammation and alveolar bone resorption via Fpr2, with improved tissue integrity and reduced inflammatory cells infiltration. Single-cell sequencing revealed elevated Fpr2 expression in RvD1-treated monocytes and downregulation of pro-inflammatory genes. RvD1 promoted M2 macrophage polarization, suppressed M1 macrophages, and reduced necroptotic cell accumulation by downregulating necroptotic-related genes. Importantly, RvD1 enhanced efferocytosis in M2 macrophages by inhibiting ADAM17 through the FPR2 receptor, thereby resolving inflammation. These effects were abolished in Fpr2Lyz2-cKO mice. The findings suggest that RvD1 mitigates periodontitis by promoting M2 macrophage polarization, reducing necroptosis, and enhancing efferocytosis. These effects are mediated via the Fpr2 receptor, indicating its potential as a therapeutic target for inflammatory periodontitis.