Myeloid-derived suppressor cells (MDSCs) are identified as a highly heterogeneous group of immature cells derived from bone marrow and play critical immunosuppressive functions in autoimmune diseases. Accumulating evidence indicates that the pathophysiology of autoimmune diseases was closely related to genetic mutations and epigenetic modifications, with the latter more common. Epigenetic modifications, which involve DNA methylation, covalent histone modification, and non-coding RNA-mediated regulation, refer to inheritable and potentially reversible changes in DNA and chromatin that regulate gene expression without altering the DNA sequence. Recently, numerous reports have shown that epigenetic modifications in MDSCs play important roles in the differentiation and development of MDSCs and their suppressive functions. The molecular mechanisms of differentiation and development of MDSCs and their regulatory roles in the initiation and progression of autoimmune diseases have been extensively studied, but the exact function of MDSCs remains controversial. Therefore, the biological and epigenetic regulation of MDSCs in autoimmune diseases still needs to be further characterized. This review provides a detailed summary of the current research on the regulatory roles of DNA methylation, histone modifications, and non-coding RNAs in the development and immunosuppressive activity of MDSCs, and further summarizes the distinct role of MDSCs in the pathogenesis of autoimmune diseases, in order to provide help for the diagnosis and treatment of diseases from the perspective of epigenetic regulation of MDSCs.
Background: Transforming growth factor-β1 (TGF-β1) has a wide range of biological functions. It antagonizes lymphocyte response, inhibits pro-inflammatory cytokines, and serves as a signal to turn off the immune response and inflammatory response. To study the correlation between TGF-β1 and T helper (Th)1/ Th2 cytokine levels in tree shrews, and to explore the effects of different levels of TGF-β1 on central venous catheter (CVC)-centered Staphylococcus epidermidis biofilm formation in tree shrews.Methods: Tree shrews were injected with different concentrations of TGF-β1, and venous blood was drawn after 48 h to measure the levels of Th1 and Th2 cytokines. A CVC was placed into the femoral vein, and TGF-β1 at different concentrations and PIA− (ATCC12228) and PIA+ (ATCC35984) standard strains of Staphylococcus epidermidis were injected into the tree shrews to establish a biomaterial-centered infection (BCI) model. After 72 h, the CVC was removed, and biofilm formation was detected using the API bacterial identification system, semi-quantitative biofilm formation assay, and scanning electron microscopy.Results: In the groups treated with TGF-β1 at different concentrations, the levels of Th1 cytokines interleukin-2 (IL-2), tumor necrosis factor (TNF), and interferon-γ (IFN-γ) were lower than those of normal group, while the levels of Th2 cytokines IL-6, IL-4 and IL-10 were higher than those of normal group. In the TGF-β1 groups at different concentrations, the positive rate of Staphylococcus epidermidis ATCC35984 biofilm formation was higher than that in non-TGF-β1 group, while there was no significant difference in the positive rate of Staphylococcus epidermidis ATCC12228 biofilm formation compared with that of the non-TGF-β1 group.Conclusions: TGF-β1 causes the imbalance of Th1/Th2 cytokines and Th1/Th2 shift in tree shrews, leading to Th1 cell-led decline in cellular immune function. TGF-β1 promotes PIA+ Staphylococcus epidermidis biofilm formation in the tree shrew BCI model, but it has no significant influence on PIA-Staphylococcus epidermidis biofilm formation on the surface of CVCs.
Background There are no reliable molecular targets for early diagnosis and effective treatment in the clinical management of diabetic kidney disease (DKD). To identify novel gene factors underlying the progression of DKD. Methods The public transcriptomic datasets of the alloxan-induced DKD model and the streptozotocin-induced DKD model were retrieved to perform an integrative bioinformatic analysis of differentially expressed genes (DEGs) shared by two experimental animal models. The dominant biological processes and pathways associated with DEGs were identified through enrichment analysis. The expression changes of the key DEGs were validated in the classic db/db DKD mouse model. Results The downregulated and upregulated genes in DKD models were uncovered from GSE139317 and GSE131221 microarray datasets. Enrichment analysis revealed that metabolic process, extracellular exosomes, and hydrolase activity are shared biological processes and molecular activity is altered in the DEGs. Importantly, Hmgcs2, angptl4, and Slco1a1 displayed a consistent expression pattern across the two DKD models. In the classic db/db DKD mice, Hmgcs2 and angptl4 were also found to be upregulated while Slco1a1 was downregulated in comparison to the control animals. Conclusions In summary, we identified the common biological processes and molecular activity being altered in two DKD experimental models, as well as the novel gene factors (Hmgcs2, Angptl4, and Slco1a1) which may be implicated in DKD. Future works are warranted to decipher the biological role of these genes in the pathogenesis of DKD.
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