DGK?± DNA vaccine relieves airway allergic inflammation in asthma model possibly via induction of T cell anergy

摘要

Induction of T cell immune tolerance is thought to be a good method for treatment of asthma. Diacylglycerol kinases alpha (DGKα), enzymes that catalyze phosphorylation of diacylglycerol to produce phosphatidic acid, could inhibit diacylglycerol (DAG)-mediated signaling following T-cell receptor engagement and prevent T cell hyperactivation, thus playing important roles in the induction of T cell anergy. In the present study, we aimed to investigate the effects of DNA vaccine encoding DGKα gene administration on allergen-induced airway allergic inflammation in the murine model of asthma. Animal models were created and plasmid containing DGKα were constructed. Cytokine production was detected after the administration of DGKα gene plasmid. Immunization of mice with alum-adsorbed ovalbumin (OVA) followed by challenged with inhalation of aerosolized OVA resulted in the development of airway allergic inflammation. Administration of DGKα gene before the aerosolized OVA challenge significantly decreased the allergic airway inflammation and eosinophil infiltration in bronchoalveolar lavage fluid (BALF). Immunization with DGKα DNA vaccine decreased OVA-specific IgE and interleukin 13 (IL-13) levels in sera, and increased the IFN-γ level in BALF. The results of the present study provide evidence for the potential utility of the administration of DGKα DNA vaccine as an approach to gene therapy for asthma.