Myeloid-derived Suppressor Cells (MDSCs) And Its Subsets In Type 1 Diabetes(T1D) Mice

ObjectTo establish a reliable model of type 1 diabetes mellitus(T1D)mice,and to dynamically monitor the proportion of myeloid-derived suppressor cells(MDSCs)and its subtypes,granulocyte myeloid-derived suppressor cells(G-MDSCs),mononuclear myeloid-derived suppressor cells(M-MDSCs),T lymphocytes in the peripheral blood and spleen,and concentration of S100A8/S100A9 in the serum of T1D mice.MethodThe T1D mice model were induced by multiple small dose STZ injections while mice in control group were treated with citrate buffer.Body weights and blood glucose levels of the mice were measured weekly.Mice were sampled at the 2nd,3rd,4th,5th and 6th weeks after the last STZ or citrate buffer administration.Percentages of MDSCs,G-MDSCs,M-MDSCs and T lymphocytes in peripheral blood and spleen,and concentrations of S100A8/S100A9 in the serum of the mice were detected.Pancreatic histopathology was recorded.The Statistical analyses were carried out by R,and difference between T1D mice and control mice were considered statistically significant when p-value was less than 0.05.Result1.T1D mice model were successfully established by STZ.2.In peripheral blood of T1D mice,percentages of MDSCs increased gradually and were significantly greater than those of the control mice at the 4th and 5th week after the final injection(P < 0.05);Percentages of G-MDSCs increased gradually and were significantly greater than those of the control mice at the 4th and 5th week after the final injection(P < 0.05);Percentage of M-MDSCs was significantly lower than that of the control group at the 3rd week after the final injection(P < 0.05).3.In the spleens of T1D mice,percentages of MDSCs were not significantly different from those of the control mice at any week after the final injection(P > 0.05);Percentage of G-MDSCs was significantly lower than that of the control mice at the 4th week after the final injection(P < 0.05);Percentage of M-MDSCs at the 4th week after the final injection was significantly lower than that of the control group(P < 0.05),while at the 5th week,was significantly greater than that of the control group(P < 0.05).4.Percentage of T lymphocytes in peripheral blood of T1D mice was significantly lower than that of the control group at the 5th week after the final injection(P < 0.05);Percentages of T lymphocytes in spleens of T1D mice were not significantly different from those of the control mice at any week after the final injection(P > 0.05);5.Pancreatic islets in T1D mice had declined and atrophied,and some were infiltrated by inflammatory cells;Cells in those islets declined too and were distorted.6.Concentration of S100A8/S100A9 in the serum of T1D mice was significantly higher than that of the control group at the 5th week after the final injection(P < 0.05).7.Concentration of S100A8/S100A9 in the serum of T1D mice was correlated with percentage of MDSCs(and its subsets)(P < 0.05).Conclusion1.Multiple small dose STZ injections is a simple and reasonable way to induce T1D mice model.2.G-MDSCs was the main subset of MDSCs in the peripheral blood of T1D mice and increased gradually with the develop of the disease.3.G-MDSCs was the main subset of MDSCs in the spleen of T1D mice;Percentages of MDSCs and its subsets showed no consistent tendency of increase or decline.4.Percentages of T lymphocytes in peripheral blood and spleens of T1D mice were not significantly different from those of the control mice.5.Atrophy and inflammatory cells infiltration were the main histopathological change of pancreatic islets of T1D mice.6.Level of S100A8/S100A9 in serum of T1D mice increased and was correlated with percentage of MDSCs in peripheral blood.