Research ArticleImmunology

Altered homeostasis and development of regulatory T cell subsets represent an IL-2R–dependent risk for diabetes in NOD mice

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Science Signaling  19 Dec 2017:
Vol. 10, Issue 510, eaam9563
DOI: 10.1126/scisignal.aam9563

IL-2 signaling and autoimmunity

Regulatory T cells (Tregs) suppress autoreactive effector T cells to prevent the occurrence of autoimmune diseases, such as type 1 diabetes (T1D). The cytokine interleukin-2 (IL-2) is critical for the development and homeostasis of Treg subsets. Polymorphisms in the genes encoding IL-2 and its receptor subunits are associated with an increased risk of developing autoimmunity. To examine the effect of decreased IL-2 signaling, Dwyer et al. expressed a signaling-defective mutant IL-2 receptor (IL-2RβY3) in T cells in NOD mice, a model of T1D. Compared to NOD mice expressing wild-type IL-2Rβ, those expressing IL-2RβY3 in their T cells had accelerated onset of T1D. This was associated with a decrease in the numbers and suppressive activity of different Treg subsets and in the infiltration of autoreactive effector T cells into the pancreas. Together, these data suggest that the use of low-dose IL-2 to therapeutically modulate different Treg subsets in the context of autoimmune disease should be evaluated.

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