Cell Reports (Apr 2012)

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

DOI
https://doi.org/10.1016/j.celrep.2012.02.007
Journal volume & issue
Vol. 1, no. 4
pp. 360 – 373

Abstract

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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 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.