1742-P: Blockade and Reversal of Autoimmunity and Type 1 Diabetes through Gene-Therapeutic and Nutritional Intervention of Elevating ω-3 PUFAs

Despite the benefit of insulin injection, blockade of autoimmune attack and regeneration of pancreatic islets remain to be the ultimate sought-after goal for the complete cure of type 1 diabetes(T1D). Long-term consumption of ω-3 polyunsaturated fatty acids (PUFAs) is known to suppress inflammatory processes, making these fatty acids candidates for both prevention and amelioration of autoimmune diseases. Herein, we explored the preventative and therapeutic effects of ω-3 PUFAs on T1D. In NOD mice, dietary intervention with ω-3 PUFAs sharply reduced the incidence of T1D, readjusted the population of Th1, Th2, Th17 and Treg, balanced the ratio of Th1/Th2, decreased the levels of such cytokines as IFN-γ, IL-17, IL-6 and TNF-α. In T1D patients, ω-3 PUFAs also regulated CD4⁺ T-cell differentiation isolated from peripheral blood mononuclear cells (PBMCs) in a manner similar to that observed in NOD mice. The regulation of CD4⁺T-cell differentiation was mediated at least in part through some of their eicosanoid derivatives and by inhibition of mTORC1. Importantly, therapeutic intervention in NOD mice through nutritional or gene-therapeutic supplementation completely normalized blood glucose and insulin levels for at least 182 days, blocked autoimmune development, prevented lymphocyte infiltration into regenerated islets, and sharply elevated expression of Pdx1 and Pax4. The findings revealed herein can potentially become a novel and cost-effective therapeutic modality in the cure of T1D.