Myeloid-derived Suppressor Cells Mitigate Inflammation in Periodontal Disease

Abstract

Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of immature, immune suppressive myeloid cells. However, their role in periodontal disease (PD), a microbially induced inflammatory oral disease, remains understudied. Here we show that gingiva (gums) from PD patients exhibit significantly higher levels of MDSC markers including Granulocytic (G)-MDSC and Monocytic (M)-MDSC subsets as well as CD4+ T cells and CD19+ B cells. Gingival MDSC subsets exhibit potent immunoregulatory activity as marked by attenuated autologous CD4+ T cells proliferation and IFN{gamma} production. In a murine model of ligature-induced periodontitis (LIP), we noticed time-dependent gingival MDSC infiltration, which correlates with CD4+ T cell and CD19+ B cell infiltration. To test whether MDSC confer immunoregulatory function in vivo, we adoptively transferred G-MDSCs and M-MDSCs in mice. Interestingly, we observed significant reduction in inflammatory marker expression (IL6, TNF-, and IL-1{beta}), infiltration of CD4+ T cells, and concomitant increase in MDSC-derived immune suppressive molecules, ARG1 and IL-10, and CD4+CD25+FoxP3+ Tregs compared to mock. Conversely, depletion of MDSC using anti-Gr1 antibody resulted in marked induction of periodontal inflammation, reduced Treg population, and significantly higher alveolar bone loss. These findings, for the first time, suggest an anti-inflammatory and osteoprotective function of MDSCs in PD and offer a promising target to treat unresolved periodontal inflammation.