UC-BSCs Exosomes Regulate Th17/Treg Balance in Patients with Systemic Lupus Erythematosus via miR-19b/KLF13

Abstract

Umbilical cord blood mesenchymal stem cells (UC-BSCs) are cells with low immunogenicity and differentiation potential, and the transfer of exosomes carried by UC-BSCs can regulate innate and adaptive immunity and affect immune homeostasis. This is an area of focus for autoimmune illnesses such as systemic lupus erythematosus (SLE). The target of this research was to investigate the immunomodulatory effect of exosomes produced from mesenchymal stem cells on SLE and its mechanism. After isolation of peripheral blood mononuclear cells (PBMC) from the SLE group and healthy group and treatment of SLE-derived PBMCs with UC-BSC-derived exosomes, the mRNA levels of corresponding factors in cells under different treatments were determined by RT-PCR, Th17/Treg content was analyzed by FCM (flow cytometry), and the targeted binding of microRNA-19b (miR-19b) to KLF13 was identified by in vitro experiments and bioinformatics analysis. The findings demonstrated that PBMC cells from SLE patients had higher proportions of Th17 subsets than the control group, whereas Treg subgroups with lower percentages were discovered. miR-19b’s expression level was markedly reduced, which was inversely associated to the concentration of KLF13. In vitro experiments show that UC-BSC-derived exosome treatment can target KLF13 expression by increasing the miR-19b level, thereby regulating Th17/Treg balance and inhibiting the expression of inflammatory factors. According to the study’s findings, SLE patients have dysregulated expression of the genes miR-19b and KLF13, and UC-BSC exosomes could regulate Th17/Treg cell balance and inflammatory factor expression in SLE patients through miR-19b/KLF13.

Mesenchymal stromal cell derived extracellular vesicles as a therapeutic tool: immune regulation, MSC priming, and applications to SLE

“…showed a lower expression of miR-19b, an imbalance between Th17 and Tregs, a much higher expression of pro-inflammatory cytokines in PBMCs from SLE patients. UC-MSC EVs treatment increased the expression of miR-19b, regulated the Th17/Tregs balance and reduced the expression of pro-inflammatory factors ( 208 ). The amount of B cells in SLE patients is significantly upregulated.…”

Mesenchymal Stromal Cell-Derived Small Extracellular Vesicles Modulate Apoptosis, TNF Alpha and Interferon Gamma Response Gene mRNA Expression in T Lymphocytes

“…Several studies demonstrated that EVs, and in particular sEVs, play a role in these transmission mechanisms by modulating mRNA expression in immune cells [ 5 , 6 , 7 , 8 , 9 , 32 ]. Furthermore, they have been shown to regulate several key biological properties in both B and T cells [ 8 , 24 , 25 , 33 ]. In our previous work, we demonstrated that bmMSC-sEVs can suppress proliferation of PBMCs, particularly B and T cells.…”

Exosomes in Action: Unraveling Their Role in Autoimmune Diseases and Exploring Potential Therapeutic Applications

“…Understanding the mechanism of miR-125b in SLE may provide exciting opportunities for developing new treatments. In vitro experiments and bioinformatics analysis of PBMCs treated with EXOs from human umbilical cord mesenchymal stem cells (UC-BSCs) revealed that upregulation of miR-19b can decrease the expression of its target gene KLF13 ( 20 ). Interestingly, an imbalance in miR-19b and KLF13 gene expression has been reported in SLE patients.…”