Aim
Myeloid-derived suppressor cells are a heterogeneous cell population that expand during several pathogenic conditions. However, their role in non-alcoholic steatohepatitis remains unclear. This study aimed to examine the systemic effects of myeloid-derived suppressor cells, to determine the role of Gr-1highLy6G+MDSCs and their correlation with the CXCL12/CXCR4 axis in non-alcoholic steatohepatitis.
Conclusions
Exogenous Gr-1highLy6G+MDSCs improved liver function during non-alcoholic steatohepatitis. The CXCR4/CXCL12 axis could be the key pathway mediating the attraction of myeloid-derived suppressor cells into the non-alcoholic steatohepatitis environment in mice.
Methods
We established a non-alcoholic steatohepatitis model and detected inflammatory factors IL-6, PGE2, and INF-γ, using an enzyme-linked immunosorbent assay. Proportions of lymphocyte subsets in peripheral blood, CD11b+Gr-1+myeloid-derived suppressor cells and its subsets in the blood, spleen, liver, and bone marrow were identified using flow cytometry. Adoptive transfer and depletion experiments for MDSCs were performed. Immunohistochemistry, migration assays, and in vivo experiments were used to analyze the role of CXCL12/CXCR4 in non-alcoholic steatohepatitis.
Results
The proportion of CD11b+Gr-1+MDSCs changed in the bone marrow, spleen, blood, and liver in the non-alcoholic steatohepatitis model. CD4+ and CD8+ T lymphocytes were significantly reduced in non-alcoholic steatohepatitis. Compared with control mice, a significant decrease in ALT and AST levels was observed in Gr-1highLy6G+MDSCs-treated model mice. The migration ability of AMD3100-treated MDSCs was significantly reduced, but was restored as CXCL12 levels increased. CXCL12 and CXCR4 protein levels increased significantly in the non-alcoholic steatohepatitis livers. Conclusions: Exogenous Gr-1highLy6G+MDSCs improved liver function during non-alcoholic steatohepatitis. The CXCR4/CXCL12 axis could be the key pathway mediating the attraction of myeloid-derived suppressor cells into the non-alcoholic steatohepatitis environment in mice.