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Papers Of The Week
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The Fox Determines T Cell Fate

Foxp3 Inhibits ROR{gamma}t-mediated IL-17A mRNA Transcription through
Direct Interaction with ROR{gamma}t
Kenji Ichiyama, Hideyuki Yoshida, Yu Wakabayashi, Takatoshi Chinen, Kazuko
Saeki, Mako Nakaya, Giichi Takaesu, Shohei Hori, Akihiko Yoshimura, and
Takashi Kobayashi
J. Biol. Chem. 2008;283 17003-17008
www.jbc.org/cgi/content/abstract/283/25/17003

こちらもぜひ

www.jbc.org/cgi/content/full/283/25/e99927

www.jbc.org/cgi/content/full/M801286200/DC1

Transforming growth factor-β1 (TGF-β1) is required to convert naïve T cells into inducible regulatory T cells (iTreg) that help maintain immune tolerance, yet TGF-β1 also induces the production of a class of helper T cells (Th17, which produce the cytokine interleukin-17) that can contribute to autoimmunity. In this Paper of the Week, Kenji Ichiyama and colleagues report on how this same factor regulates two opposing fates. They found that the transcriptional repressor protein Foxp3 promotes the induction regulatory T cells by suppressing Th17 induction. Foxp3 can directly interact with the retinoic acid-related orphan receptor t (RORt), another key Th17 activator that binds to the IL-17A gene promoter, and subsequently inhibit the expression of the signature cytokine IL-17. Ichiyama and colleagues also observed that another cytokine, interleukin-6, reduced Foxp3 expression, thus paving the way for RORt to stimulate production of IL-17 and shift T cell development to the helper pathway