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An IL-2 mutein engineered to promote expansion of regulatory T cells arrests ongoing autoimmunity in mice

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Science Immunology  14 Aug 2020:
Vol. 5, Issue 50, eaba5264
DOI: 10.1126/sciimmunol.aba5264

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Delivering IL-2 to Tregs

Interleukin-2 (IL-2) not only promotes activation and expansion of conventional T cells but also plays a crucial role in regulating homeostasis and functions of regulatory T (Treg) cells. As expression of the high-affinity IL-2 receptor is largely restricted to Treg cells, engineering IL-2 variants, called muteins, that selectively bind to the high-affinity IL-2 receptor and potentiate Treg functions can be used in the treatment of autoimmune diseases. Here, Khoryati et al. have engineered a murine IL-2 mutein that selectively promotes expansion of Treg cells. They demonstrate that administration of this IL-2 mutein resolved ongoing diabetes in nonobese diabetic mice. This proof-of-principle study raises the possibility that engineered human IL-2 muteins could be used in the treatment of autoimmune diseases.

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