Hippo Kinases Mst1 and Mst2 Sense and Amplify IL-2R−STAT5 Signaling in Regulatory T Cells to Establish Stable Regulatory Activity

Treg cells respond to low IL-2 levels, but how STAT5 is activated under these conditions remains uncertain. Shi et al. demonstrate that the serine/threonine kinases Mst1 and Mst2 sense IL-2 signals to promote STAT5 activation to maintain Treg cell homeostasis, lineage stability, and the highly suppressive phosphorylated-STAT5+ Treg cell subpopulation. Therefore, a non-canonical Hippo pathway orchestrates IL-2−STAT5 signaling selectively in Treg cells.

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