The ability of dendritic cells to prevent diabetes development in NOD mice depends on their production of high levels of IL‐10 versus low levels of IL‐12

Abstract

NOD mice, similar to diabetic patients, exhibit various defects in different types of immune cells, including dendritic cells (DC) that produce pro‐inflammatory cytokines, and regulatory T cells. Recognition of TLR2 can lead to immune evasion of various microorganisms via induction of tolerogenic APC and regulatory cells. The goal of this study was to induce tolerogenic NOD DC able to prevent diabetes. DC were stimulated for 24 hrs with two TLR2 agonists, lipoteichoic acid (LTA) from S. aureus and Lactobacillus. DC stimulated with LTA produced 50 times more IL‐12 than IL‐10, and mediated acceleration of diabetes development when transferred into NOD mice. In contrast, high doses of Lactobacilli (LC) favored the production of IL‐10 versus IL‐12. Transfer of DC treated with high‐dose LC, not low‐dose LC, into NOD mice delayed diabetes onset and decreased diabetes incidence. Interestingly, DC treated with high‐dose LC produced 5 times more IL‐10 than those treated with low‐dose LC. Finally, significant increases in IL‐10 levels were detected in most of the samples from LC DC‐injected NOD mice. These data indicate that the levels of IL‐10 versus IL‐12 produced by DC cultured with various stimuli correlates with the ability of those cells to prevent diabetes in NOD mice. IL‐10 may play a significant role in diabetes prevention either directly, by suppressing pro‐inflammatory responses, and/or by inducing regulatory cells.