Journal
CELL REPORTS
Volume 1, Issue 4, Pages 360-373Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2012.02.007
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Funding
- CREST from Japan Science and Technology Agency
- Japan Society for the Promotion of Science [21790476]
- The Takeda Science Foundation
- The Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Ministry of Health, Labour and Welfare, Japan
- Ministry of Education, Culture, Sports, Science and Technology, Japan [20060021]
- Grants-in-Aid for Scientific Research [23650593, 21390290, 23790546, 23390086, 22229004, 23130507, 24790479, 20060021, 22590439, 21790476, 24790967, 22790906] Funding Source: KAKEN
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The PI3K-Akt-mTORC1 axis contributes to the activation, survival, and proliferation of CD4(+) T cells upon stimulation through TCR and CD28. Here, we demonstrate that the suppression of this axis by deletion of p85 alpha or PI3K/mTORC1 inhibitors as well as T cell-specific deletion of raptor, an essential component of mTORC1, impairs Th17 differentiation in vitro and in vivo in a S6K1/2-dependent fashion. Inhibition of PI3K-Akt-mTORC1-S6K1 axis impairs the downregulation of Gfi1, a negative regulator of Th17 differentiation. Furthermore, we demonstrate that S6K2, a nuclear counterpart of S6K1, is induced by the PI3K-Akt-mTORC1 axis, binds ROR gamma, and carries ROR gamma to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.
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