Foxp3 Inhibits RORγt-mediated IL-17A mRNA Transcription through Direct Interaction with RORγt*
| Autor: | Yu Wakabayashi, Kenji Ichiyama, Takashi Kobayashi, Kazuko Saeki, Hideyuki Yoshida, Takatoshi Chinen, Giichi Takaesu, Mako Nakaya, Akihiko Yoshimura, Shohei Hori |
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| Rok vydání: | 2008 |
| Předmět: |
Transcription
Genetic Receptors Retinoic Acid T-Lymphocytes medicine.medical_treatment T cell Molecular Sequence Data chemical and pharmacologic phenomena Biology Models Biological Biochemistry Mice RAR-related orphan receptor gamma Transcription (biology) Sequence Homology Nucleic Acid medicine Animals Humans Promoter Regions Genetic Receptor Molecular Biology Orphan receptor Binding Sites Receptors Thyroid Hormone Base Sequence Interleukin-17 FOXP3 Interleukin Forkhead Transcription Factors hemic and immune systems Cell Biology Nuclear Receptor Subfamily 1 Group F Member 3 Molecular biology Cytokine medicine.anatomical_structure Protein Binding |
| Zdroj: | Journal of Biological Chemistry. 283:17003-17008 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m801286200 |
| Popis: | The cytokine, transforming growth factor-beta1 (TGF-beta1), converts naive T cells into regulatory T cells that prevent autoimmunity. However, in the presence of interleukin (IL)-6, TGF-beta1 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-beta1 and IL-6 determine such a distinct fate. Here we found that a master regulator for Th17, retinoic acid-related orphan receptor gammat (RORgammat), was rapidly induced by TGF-beta1 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 RORgammat binding is sufficient for activation of the minimum promoter in the HEK 293T cells. RORgammat-mediated IL-17A promoter activation was suppressed by forced expression of Foxp3. Foxp3 directly interacted with RORgammat through exon 2 region of Foxp3. The exon 2 region and forkhead (FKH) domain of Foxp3 were necessary for the suppression of RORgammat-mediated IL-17A promoter activation. We propose that induction of Foxp3 is the mechanism for the suppression of Th17 and polarization into inducible Treg. |
| Databáze: | OpenAIRE |
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