An involvement of ribonuclease L in Parkinson's disease via modulating the Th17/Treg balance by microRNA-7.

RNase L is an interferon-regulated endoribonuclease that plays a critical role in antiviral immunity and inflammation. Increased mRNA levels of RNase L have been observed in peripheral blood cells of patients with early-stage idiopathic Parkinson's disease (PD). An imbalance between Th17 and Treg cells, which is implicated in PD pathogenesis, is well recognized. In this study, elevated expression of RNase L protein was confirmed in peripheral blood CD4+ T cells from PD patients. Amelioration of MPTP-induced PD was observed in RNase L-/- and RNase Lflox/flox-CD4cre mice. Increased Treg cells and decreased Th17 cells were found to inhibit PD progression. Additionally, transfusion of RNase L-/- Treg cells into PD mice exerted an ameliorative effect. RNase L deficiency directly promoted Treg cell differentiation and inhibited Th17 cells ex vivo. Conversely, ectopic expression of RNase L promoted Th17 cell differentiation whereas inhibiting Treg cells. Transcriptome analysis revealed that miR-7 was upregulated in RNase L-/- Treg cells and effectively suppressed Th17 cell differentiation by targeting the 3'-UTR of IL-17 A. Thus, novel RNase L inhibitors could offer therapeutic potential for PD treatment.