PI3K-Akt-mTORC1-S6K1/2 Axis Controls Th17 Differentiation by Regulating Gfi1 Expression and Nuclear Translocation of RORγ

Yutaka Kurebayashi, Shigenori Nagai, Ai Ikejiri, Masashi Ohtani, Kenji Ichiyama, Yukiko Baba, Taketo Yamada, Shohei Egami, Takayuki Hoshii, Atsushi Hirao, Satoshi Matsuda, Shigeo Koyasu

Research output: Contribution to journalArticlepeer-review

195 Citations (Scopus)

Abstract

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 p85α 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 RORγ, and carries RORγ to the nucleus. These results point toward a pivotal role of PI3K-Akt-mTORC1-S6K1/2 axis in Th17 differentiation.

Original languageEnglish
Pages (from-to)360-373
Number of pages14
JournalCell Reports
Volume1
Issue number4
DOIs
Publication statusPublished - 2012 Mar 19

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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