Myeloid-derived suppressor cells mitigate inflammation in periodontal disease.

Myeloid-derived suppressor cells (MDSCs) are immature, immunosuppressive myeloid cells whose role in periodontal disease (PD) is not well defined. Here, we show that gingiva from PD patients exhibit increased infiltration of MDSCs, including granulocytic (G-MDSC) and monocytic (M-MDSC) subsets, alongside elevated CD4+ T cells and CD19+ B cells. Functionally, these MDSC subsets suppress autologous CD4+ T cell proliferation in co-culture, confirming their immunoregulatory capacity. In a murine ligature-induced periodontitis (LIP) model, both gingival MDSC subsets increased over time and correlated with CD4+ T cell and CD19+ B cell infiltration. Adoptive transfer of G-MDSCs and M-MDSCs into LIP mice reduced gingival CD4+ T cell infiltration and pro-inflammatory cytokines, while increasing arg1, Il-10, and CD4+CD25+FoxP3+ Tregs. In contrast, anti-Gr-1 depletion exacerbated periodontal inflammation, reduced Treg counts, and increased alveolar bone loss. Collectively, these findings identify anti-inflammatory and osteoprotective roles for MDSCs in PD and support their therapeutic potential for periodontal inflammation.