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:10.1016/j.celrep.2012.02.007

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

Affiliations

Yutaka Kurebayashi: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Shigenori Nagai: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Ai Ikejiri: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Masashi Ohtani: Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University, Moriguchi, Osaka 570-8586, Japan
Kenji Ichiyama: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Yukiko Baba: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Taketo Yamada: Department of Pathology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Shohei Egami: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan
Takayuki Hoshii: Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan
Atsushi Hirao: Division of Molecular Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan
Satoshi Matsuda: Department of Cell Signaling, Institute of Biomedical Science, Kansai Medical University, Moriguchi, Osaka 570-8586, Japan
Shigeo Koyasu: Department of Microbiology and Immunology, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan

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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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