Mesenchymal stem cells negatively regulate CD4(+) T cell activation in patients with primary Sjögren syndrome through the miRNA-125b and miRNA-155 TCR pathway

Treatment with mesenchymal stem cells (MSCs) has been revealed to suppress CD4(+) T cells and autoimmunity in both mouse models and patients with primary Sjögren syndrome (pSS); however, the underlying mechanism remains unclear. MicroRNAs (miRNAs or miRs) mediate CD4(+) T cell activation, but the mechanism is not understood, particularly for CD4(+) T cells treated with MSCs. Characterization of miRNAs may reveal pSS pathogenesis, guide MSC treatment and provide more personalized management options. The present study aimed to perform an miRNome analysis of quiescent and T cell receptor (TCR)-activated CD4(+) T cells treated with MSCs via miRNA profiles and bioinformatics. Following 72 h of co-culture, MSCs inhibited TCR-induced CD4(+) T cell activation and decreased IFN-γ levels. The numbers of aberrant miRNAs in pSS naïve (vs. healthy naïve), pSS activation (vs. pSS naïve), MSC treatment and pre-IFN-γ MSC treatment (vs. pSS activation) groups were 42, 55, 27 and 32, respectively. Gene enrichment analysis revealed that 259 pathways were associated with CD4(+) T cell stimulation, and 240 pathways were associated with MSC treatment. Increased miRNA-7150 and miRNA-5096 and decreased miRNA-125b-5p and miRNA-22-3p levels in activated CD4(+) T cells from patients with pSS were reversed by MSC treatment. Notably, the proliferation of CD4(+) T cells and CD4(+) IFN-γ(+) cells, expression levels of miRNA-125b-5p and miRNA-155 in CD4(+) T cells and supernatant IFN-γ secretion were associated with disease activity. miRNA may play a vital role in MSC treatment for activated CD4(+) T cells. The results indicated that the expression levels of miRNA-125b-5p and miRNA-155 in TCR-activated CD4(+) T cells from patients with pSS may provide insight regarding autoimmune diseases and offer a novel target for prospective treatment. Therefore, these results may be crucial in providing MSC treatment for pSS.