124 MicroRNA-3926 promotes apoptosis of SLE CD4+ T cells through inhibiting autophagy by targeting ATG5

Abstract

Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by impaired T lymphocyte homeostasis, resulting in increased apoptosis and T cell hyperactivation. A wealth of studies has implicated autophagy in the pathogenesis of SLE. However, the mechanisms underlying the regulation of autophagy and apoptosis in SLE remain unclear. The aim of this study was to explore the role of miR-3926 in crosstalk of autophagy and apoptosis in SLE. By qRT-PCR and western blot, we found that the expression of miR-3926 was significantly up-regulated in SLE CD4+ T cells compared with in healthy donors and was inversely correlated with the expression of ATG5, whereas ATG5 mRNA and protein expression was down-regulated. Luciferase reporter assays demonstrated that miR-3926 directly targeted ATG5 mRNA. Up-regulation of miR-3926 by mimic transfection inhibited autophagy activity in healthy donor CD4+ T cells by down-regulating ATG5 expression, and the modulated autophagy was closely associated with both caspase-mediated apoptosis and T cell overactivation observed in SLE, whereas miR-3926 inhibitors led to the complete opposite effects in SLE CD4+ T cells. Collectively, our data suggest that miR-3926 promotes apoptosis in SLE CD4+ T cells through inhibiting autophagy and contributes to T cell autoreactivity in SLE by directly targeting ATG5. Our findings provide new insight into the molecular mechanisms underlying CD4+ T cell autophagy and apoptosis crosstalk, and suggest a possible efficacious adjuvant therapy for SLE patients.