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

Cells. 2022 Dec 19;11(24):4123. doi: 10.3390/cells11244123.

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.

Keywords: exosomes; inflammatory factors; mathematical and statistical analysis; peripheral blood mononuclear cells; systemic lupus erythematosus; umbilical cord blood mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism
  • Exosomes* / metabolism
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Lupus Erythematosus, Systemic*
  • MicroRNAs* / metabolism
  • Repressor Proteins / metabolism
  • T-Lymphocytes, Regulatory

Substances

  • Cell Cycle Proteins
  • KLF13 protein, human
  • Kruppel-Like Transcription Factors
  • MicroRNAs
  • Repressor Proteins
  • MIRN19 microRNA, human

Grants and funding

Natural Science Foundation of Zhejiang Province, China (Grant/Award Number: LY20H100002), Medical Science Research Foundation of Zhejiang Province, China (Grant/Award Number: 2020KY634).