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| Status |
Public on Nov 08, 2018 |
| Title |
Hippo kinases Mst1 and Mst2 sense and amplify IL-2R−STAT5 signaling in Treg cells to establish stable regulatory activity |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Interleukin-2 (IL-2) and downstream transcription factor STAT5 are important for maintaining regulatory T (Treg) cell homeostasis and function. Tregs can respond to low levels of IL-2, but the mechanisms by which STAT5 is activated during partial IL-2 deficiency remain uncertain. We identified the serine-threonine kinase Mst1 as a signal-dependent amplifier of IL-2−STAT5 activity in Tregs. Tregs had high Mst1 and Mst2 (Mst1−Mst2) activity that was crucial to prevent tumor resistance and autoimmunity. Mechanistically, Mst1−Mst2 sensed IL-2 signals to promote the STAT5 activation necessary for Treg cell homeostasis and lineage stability, and maintain the highly suppressive phophorylated-STAT5+ Treg cell subpopulation. Unbiased quantitative proteomics revealed an association of Mst1 with the cytoskeletal DOCK8−LRCHs module that shaped activity Rho-family GTPase Rac activity, which in turn mediated STAT5 activation in Tregs. Collectively, IL-2−STAT5 signaling critically depends upon Mst1−Mst2 functions to maintain a stable Treg cell pool and immune tolerance.
We used microarrays to compare the global transcription profiles of WT and Mst1/Mst2-null Treg cell populations
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| Overall design |
In total 9 samples were analyzed: Treg cells (WT, n = 5; Mst1/Mst2-null, n = 4).
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| Contributor(s) |
Shi H, Liu C, Neale G, Chi H |
| Citation(s) |
30413360 |
| |
| Submission date |
Oct 01, 2018 |
| Last update date |
Nov 13, 2018 |
| Contact name |
Geoffrey Neale |
| E-mail(s) |
geoffrey.neale@stjude.org
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| Organization name |
St Jude Childrens Research Hospital
|
| Department |
Hartwell Center
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| Street address |
262 Danny Thomas Place
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| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (1) |
| GPL16570 |
[MoGene-2_0-st] Affymetrix Mouse Gene 2.0 ST Array [transcript (gene) version] |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA494226 |
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