MiR-153-3p induces immune dysregulation by inhibiting PELI1 expression in umbilical cord-derived mesenchymal stem cells in patients with systemic lupus erythematosus.

Abstract

Mesenchymal stem cells (MSCs) are identified as a promising tool for the treatment of autoimmune diseases, and several microRNAs (miRNAs) are shown to exhibit vital roles in immune diseases. However, their function and mechanism in systemic lupus erythematosus (SLE) is still unclear. The qRT-PCR analysis was employed to investigate level of miR-153-3p. Subsequently, western blot and luciferase reporter assays were carried out to determine miR-153-3p targets. Cell proliferation and migration were determined using EdU proliferation assays and transwell migration assays. Apoptosis levels were evaluated by annexin V staining and flow cytometry. We used human umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation to treat MRL/lpr mice. It was observed that miR-153-3p was upregulated in patients with SLE, and was closely related to SLE disease activity. Overexpression of miR-153-3p decreased UC-MSCs proliferation and migration, and weakened UC-MSCs-mediated decrease of follicular T helper (Tfh) cells and increase of regulatory T (Treg) cells through repressing PELI1 in vitro. We also found that PELI1 overexpression abolished the function of miR-153-3p on UC-MSCs. Furthermore, miR-153-3p overexpression weakened the therapeutic effect of UC-MSCs in MRL/lpr mice in vivo. Taken together, all data suggested that miR-153-3p is a mediator of SLE UC-MSCs regulation and may function as a new therapeutic target for the treatment of lupus.