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

Interleukin-2 (IL-2) and downstream transcription factor are important for maintaining regulatory T (Treg) cell homeostasis and function. Treg cells can respond to low IL-2 levels, but the mechanisms of duanyu18135 activation during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of activity in Treg cells. High Mst1 and Mst2 (Mst1-Mst2) activity in Treg cells was crucial to prevent tumor resistance and autoimmunity. Mechanistically, Mst1-Mst2 sensed IL-2 signals to promote the duanyu18135 activation necessary for Treg cell homeostasis and lineage stability and to maintain the highly suppressive Treg cell subpopulation. Unbiased quantitative proteomics revealed association of Mst1 with the cytoskeletal DOCK8-LRCHs module. Mst1 deficiency limited Treg cell migration and access to IL-2 and activity of the small GTPase Rac, which mediated downstream duanyu18135 activation. Collectively, IL-2-duanyu18135 signaling depends upon Mst1-Mst2 functions to maintain a stable Treg cell pool and immune tolerance. Copyright © 2018 Elsevier Inc. All rights reserved.

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