Novel therapy for allergic disease through gene silencing of CD40 (37.7)

Abstract

Abstract Gene silencing is a potent, selective, and easily-inducible method for specifically blocking expression of desired genes. Gene silencing strategies have been successfully tested in animal models of various diseases. However, the therapeutic potential of gene silencing allergic diseases has not yet been reported. CD40 is an important costimulatory molecule that plays a critical role in immune responses. We attempted to develop a new therapy for allergic diseases through gene silencing using a short hairpin siRNA-expressing vector (shRNA) specific to CD40. The allergic mouse model was made by intraperitoneal immunization with ovalbumin (OVA), followed by intranasal challenges with the same antigen. CD40 shRNA was administered before or after OVA immunization. CD40 shRNA treatment reduced CD40 expression in splenic DC, remarkably reduced nasal allergic symptoms, and decreased nasal eosinophilia. The OVA-specific T cell response was inhibited after CD40 shRNA treatment. Additionally, anti-OVA specific IgE was significantly decreased in CD40-shRNA treated mice, as detected by ELISA. The production of IL-4 and IL-5 was suppressed in the CD40-shRNA treated mice. Finally, CD40 shRNA facilitated the generation of regulatory T cells, in particular, the CD4+CD25+Foxp3+ subset of cells. This study, for the first time, has demonstrated a novel therapy for allergic disease through gene silencing.