TGF-β-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation

Yutaka Kurebayashi, Yukiko Baba, Akiko Minowa, Niken Adiba Nadya, Miyuki Azuma, Akihiko Yoshimura, Shigeo Koyasu, Shigenori Nagai

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Transforming growth factor-β (TGF-β) is a pivotal cytokine in the differentiation of regulatory T cells, and Foxo transcription factors positively regulate this process. On the other hand, the function of Foxo transcription factors is negatively regulated by PI3K/Akt signaling, which is activated by TGF-β in many types of cells; yet the role of TGF-β in Akt activity and its downstream substrates in CD4+ T cells, including Foxo transcription factors, remains to be determined. Herein, we demonstrate that TGF-β selectively induces Akt phosphorylation at Ser473 but not at Thr308 in a class IA PI3K-dependent manner in CD4+ T cells, resulting in the phosphorylation and inhibition of Foxo transcription factors and negatively regulating the differentiation of induced regulatory T cells (iTregs). These observations reveal a novel negative regulatory mechanism involving Akt and Foxo transcription factors induced by TGF-β in the iTreg differentiation process.

Original languageEnglish
Pages (from-to)114-119
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume480
Issue number1
DOIs
Publication statusPublished - 2016 Nov 4

Keywords

  • Akt
  • Foxo
  • PI3K
  • TGF-β
  • Treg

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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