Targeting the IL-10 Pathway by RNA Interference Has Beneficial Effects on the Development of Experimental Lupus

Abstract

Results from patients with systemic lupus erythematosus (SLE) and from mice suffering from a lupus-like disease suggest that the IL-10 pathway is involved in pathogenesis, and that this cytokine could represent a target for managing SLE development. In this study, we constructed JC virus-like particles (VLP) expressing IL-10-specific short hairpin RNAs (shRNAs) that efficiently silenced IL-10 gene expression. In mice, a single injection of this preparation dramatically reduced serum levels of ILIO. We tested the preventive effect of this vector expressing anti-IL-10 shRNAs in female (NZBxNZW) F, mice. Weekly intraperitoneal injections decreased the incidence and severity of proteinuria, and prolonged lifespan, with reduced IL-10 production. Our data demonstrate that the IL-10 pathway plays a chief role in lupus pathogenesis. It indicates that JC virus-like particles represent a potent vector for delivering interfering RNA in vivo. They suggest that RNA interference targeting IL-10 is an effective strategy to silence the IL-10 pathway, and possesses a therapeutic potential that could be useful in the management of SLE and, possibly, other immune-mediated disorders.