IL-2 production by dendritic cells promotes Foxp3⁺regulatory T-cell expansion in autoimmune-resistant NOD congenic mice

Abstract

Il2 allelic variation in non-obese diabetic mice imparts marked resistance to type 1 diabetes. IL-2 is pivotal for the fitness and homeostasis of Foxp3(+) regulatory T (T(reg)) cells, and the Idd3(B6) locus augments IL-2 production by effector T cells, which in turn enhances the potency of T(reg) cell functions. Given the important role dendritic cells (DCs) play in T(reg) cell-mediated tolerance induction, we hypothesized that DCs from Idd3(B6) congenic mice contribute to increased T(reg) cell activity. Here, we observed that CD11c(+) DCs, harboring protective Idd3(B6) genes, are endowed with the capacity to secrete IL-2, enabling them to preferentially promote T(reg) cell functions in vitro and in vivo. Our results show that Il2 gene variation may imprint DCs to favor T-cell regulation of autoimmunity.