Characterization of Liver Monocytic Myeloid-Derived Suppressor Cells and Their Role in a Murine Model of Non-Alcoholic Fatty Liver Disease

Myeloid-derived suppressor cells (MDSCs) are potent suppressors of T cell immunity in tumors and inflammatory diseases. They are identified by surface expression of CD11b(+)Gr1(+) in mice, and CD11b(+)Gr1(+) cells accumulate in the livers of obese mice. However, many myeloid cells share these CD11b(+)Gr1(+) markers. Accordingly, the aim of this study was to identify the authentic phenotype of MDSCs and investigate their functions in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were divided into 2 diet groups: a normal control group and high-fat group to induce NAFLD. We demonstrated that monocytic CD11b(+)Gr1(dim) cells could be further divided into 2 populations based on side scatter (SSC) during flow cytometry. We found that SSC(low)CD11b(+)Gr1(dim) cells accumulated in the livers of NAFLD mice over time, and that these cells were recruited by the chemokine CCL2 and its receptor CCR2 and might expand in the liver via macrophage colony-stimulating factor stimulation. Furthermore, SSC(low)CD11b(+)Gr1(dim) cells had a strong suppressive ability on T cells; this effect was not observed for SSC(high)CD11b(+)Gr1(dim) cells, and was dependent on nitric oxide production by inducible nitric oxide synthase. Our findings demonstrate that SSC(low)CD11b(+)Gr1(dim) cells represent authentic MDSCs in NAFLD livers, and might serve an important negative feedback function in liver inflammation.