Let-7a Inhibits T-Cell Proliferation and IFN-γ Secretion by Down-Regulating STAT3 Expression in Patients with Psoriasis

Abstract

Objective: This study aimed to explore the effects of STAT3 targeting by let-7a on T-cell proliferation and IFN-γ secretion in psoriasis.

Methods: From January 2013 to January 2015, 40 patients with psoriasis (psoriasis group) and 38 volunteers undergoing plastic surgery (control group) were enrolled in this study. Pearson correlation analysis was performed to evaluate the correlation between let-7a and STAT3 expression. T-cells were isolated and subjected to different transfection methods. A dual luciferase reporter assay was carried out to confirm STAT3 as a target gene of let-7a. Let-7a, STAT3 and IFN-γ mRNA expression was detected by quantitative real-time fluorescent polymerase chain reaction (qRT-PCR), and pSTAT3 protein levels were determined by Western blot. T-cell proliferation was evaluated with a cell counting kit-8 (CCK-8) assay.

Results: The level of STAT3 mRNA and pSTAT3 was higher, but let-7a expression was lower in the psoriasis group than the control group. Pearson correlation analysis indicated that STAT3 expression was negatively correlated with let-7a expression. T-cells transfected with inhibitors exhibited greater IFN-γ mRNA expression and T-cell proliferation than transfected T-cells and T-cells transfected with a non-sense sequence, while T-cells transfected with let-7a mimics exhibited lower IFN-γ mRNA expression and T-cell proliferation than transfected T-cells and T-cells transfected with a non-sense sequence. This suggested that siRNA-STAT3 could reverse the increase in IFN-y mRNA expression and T-cell proliferation induced by let-7a inhibitors.

Conclusion: Our results demonstrated that let-7a inhibits T-cell proliferation and IFN-γ secretion by down-regulating STAT3 in psoriasis.

Keywords: Interferon-γ; Let-7a; Proliferation; Psoriasis; STAT3; T-cell.