Myeloid-derived suppressor cells suppress CD4+ T cell activity and prevent the development of type 2 diabetes

Abstract

CD4⁺ T cells play an important role in the progression of type 2 diabetes mellitus (T2DM). It is known that T cell responses can be suppressed by myeloid-derived suppressor cells (MDSCs). In this study, we aimed to explore the potential role of MDSCs in the progression of T2DM, and to examine whether the underlying mechanism was associated with CD4⁺ T cells. Peripheral blood samples were obtained from T2DM patients and healthy controls, as well as C57BL6J db/db mice and control heterozygous (db/-) mice. The frequency of MDSCs and CD4⁺ T cells was analyzed using flow cytometry. Serum levels of the cytokines interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were quantified using ELISA kits. Cell proliferation was assessed using carboxyfluorescein succinimidyl ester (CFSE) labeling. In addition, the severity of insulitis was assessed using H&E staining of the pancreata. The data showed an increased frequency of CD11b⁺/CD33⁺ MDSCs and CD4⁺ T cells in the peripheral blood of T2DM patients. In addition, there were decreased IL-4 level and increased TNF-α and IFN-γ levels in the serum from T2DM patients. In db/db mice, an increased frequency of CD11b⁺/Gr-1⁺ MDSCs and CD4⁺ T cells was found in splenocytes, as well as in the peripheral blood. MDSCs inhibited the proliferation and modulated the cytokine secretion of CD4⁺ T cells in vitro and delayed the development of diabetes in NOD/SCID mice. In conclusion, MDSCs suppress CD4⁺ T cell activity and prevent the development of T2DM.

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