The effect of human umbilical cord mesenchymal stem cells on miRNA profile of activated peripheral blood CD4+ T cells from patient with primary Sjögren's syndrome

Objective To investigate how human umbilical cord mesenchymal stem cells (MSCs) in vitro regulate the miRNA profile of activated peripheral blood CD4+ T cells from patient with primary Sjogren's syndrome (pSS). Methods Peripheral blood CD4+ T cells from patient with pSS were sorted and divided into healthy naive group, pSS naive group, pSS activated group, MSC treatment group and MSC (pre-stimulated by IFN-γ) treatment group. CD4+ T cells were counted. MiRNA microarray technology was used to detect the expression profile of CD4+ T cells, and the expression of miRNA125b and miRNA155 was verified by real time quantification-polymerase chain reaction (RT-PCR). Mean in groups were compared using ANOVA, and multiple comparisons were used with LSD method. Results Both MSCs and IFN-γ-MSCs could inhibit the proliferation of activated CD4+ T cells in a MSC-dependent manner, but there was no significant difference between two groups. Microarray analysis found that the differentially enriched miRNAs in pSS naive (vs healthy naive), pSS activation (vs pSS naive), MSC treatment (vs pSS activation) and pre-IFN-γ MSC treatment (vs pSS activation) were 42 miRNAs, 56 miRNAs, 21 miRNAs and 24 miRNAs, respectively. Furthermore, the expressions of miRNA125b and miRNA155 were verified by RT-PCR and found that miRNA125b relative level in 5 groups was 1.02 ± 0.13, 0.80 ± 0.11, 0.44 ± 0.17, 0.76 ± 0.17 and 0.81 ± 0.15 (F=18.32, P<0.01), and miRNA155 was 1.5 ± 0.8, 3.9 ± 1.3, 8.4 ± 2.6, 10.1 ± 4.2 and 11.2 ± 5.0 (F=26.65, P<0.01). Conclusion MSCs can regulate miRNA profile of activated CD4+ T cells in peripheral blood of patient with pSS, and partially reverse down-regulated miR-125b in activated CD4+ T cells, which may play a regulatory role in inhibiting the activation of CD4+ T cells by MSCs. Key words: Sjogren's syndrome; Mesenchymal stem cells; CD4-positive T-lymphocytes