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

9 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

Fingerprint

Phosphorylation
T-cells
Transforming Growth Factors
Regulatory T-Lymphocytes
Cell Differentiation
Transcription Factors
Phosphatidylinositol 3-Kinases
T-Lymphocytes
Cytokines
Substrates

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

TGF-β-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation. / Kurebayashi, Yutaka; Baba, Yukiko; Minowa, Akiko; Nadya, Niken Adiba; Azuma, Miyuki; Yoshimura, Akihiko; Koyasu, Shigeo; Nagai, Shigenori.

In: Biochemical and Biophysical Research Communications, Vol. 480, No. 1, 04.11.2016, p. 114-119.

Research output: Contribution to journalArticle

Kurebayashi, Yutaka ; Baba, Yukiko ; Minowa, Akiko ; Nadya, Niken Adiba ; Azuma, Miyuki ; Yoshimura, Akihiko ; Koyasu, Shigeo ; Nagai, Shigenori. / TGF-β-induced phosphorylation of Akt and Foxo transcription factors negatively regulates induced regulatory T cell differentiation. In: Biochemical and Biophysical Research Communications. 2016 ; Vol. 480, No. 1. pp. 114-119.
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