Gut bacteria modulation of antigen presenting cells in a mouse model of autoimmune diabetes. (THER5P.915)

Abstract

Abstract T1D is an autoimmune disease whereby the beta cells of the pancreas are destroyed, resulting in the inability to self-regulate blood glucose. While genetics play a role, the contribution of environmental factors such as gut bacteria have also been implicated. Notably, it was shown that the oral administration of L. johnsonii N6.2 (LjN6.2) conveyed diabetes resistance to diabetes prone rodents while a second strain, Lactobacillus reuteri TD1, had no effect. However, the exact mechanisms of microbiota action on diabetes prevention remain poorly understood. As it has been shown that defective antigen presentation by dendritic cells (DC) contributes to T1D progression, we tested the hypothesis that gut flora can serve to modulate DC maturation. We observed that the administration of LjN6.2 to NOD leukocytes in vitro mediated increases in CD11c+MHCII+ DC. Moreover, LjN6.2 facilitated enhanced myeloid dendritic cell maturation denoted by the increase in number of CD8alo DEC205lo that were comparable to levels present in NOR mice. In addition, LjN6.2 also increased IL6 production. This study highlights the role of gut bacteria in autoimmunity as a critical component for T1D therapeutic strategies and might be used to extrapolate treatment approaches in humans in the future.