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.

Keywords::

• Foxp3
• IL-2
• T_reg cells
• diabetes
• NOD mice

Acknowledgements

This work was supported from the grants of CIHR (MOP67211) and CDA (#GA-3-05-1898-CP). C.A.P. holds the Canada Research Chair.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.