Foxp3 inhibits RORγt-mediated IL-17A mRNA transcription through direct interaction with RORγt

Kenji Ichiyama, Hideyuki Yoshida, Yu Wakabayashi, Takatoshi Chinen, Kazuko Saeki, Mako Nakaya, Giichi Takaesu, Shohei Hori, Akihiko Yoshimura, Takashi Kobayashi

Research output: Contribution to journalArticlepeer-review

366 Citations (Scopus)


The cytokine, transforming growth factor-β1 (TGF-β1), converts naive T cells into regulatory T cells that prevent autoimmunity. However, in the presence of interleukin (IL)-6, TGF-β1 has also been found to promote differentiation into IL-17-producing helper T (Th17) cells that are deeply involved in autoimmunity and inflammation. However, it has not been clarified how TGF-β1 and IL-6 determine such a distinct fate. Here we found that a master regulator for Th17, retinoic acid-related orphan receptor γt (RORγt), was rapidly induced by TGF-β1 regardless of the presence of IL-6. IL-6 reduced Foxp3 expression, and overexpression of Foxp3 in a T cell line resulted in a strong reduction of IL-17A expression. We have characterized the IL-17A promoter and found that RORγt binding is sufficient for activation of the minimum promoter in the HEK 293T cells. RORγt-mediated IL-17A promoter activation was suppressed by forced expression of Foxp3. Foxp3 directly interacted with RORγt through exon 2 region of Foxp3. The exon 2 region and forkhead (FKH) domain of Foxp3 were necessary for the suppression of RORγt-mediated IL-17A promoter activation. We propose that induction of Foxp3 is the mechanism for the suppression of Th17 and polarization into inducible Treg.

Original languageEnglish
Pages (from-to)17003-17008
Number of pages6
JournalJournal of Biological Chemistry
Issue number25
Publication statusPublished - 2008 Jun 20

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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