Transcriptional Regulation of Foxp3 Gene: Multiple Signal Pathways on the Road

Foxp3, forkhead/winged helix transcription factor 3, is a master transcription factor for the development and function of regulatory T cells. Foxp3 has been proved to be associated with immunoregulation, autoimmune diseases, infections, and tumor immune evasion/escape. Foxp3 regulates other critical gene transcriptions. However, the mechanism how the transcription of Foxp3 itself is regulated remains partly clear. In this article, we provided an overview of the current understanding of the transcriptional regulation of Foxp3 gene, including signaling pathways initiated by TCR, IL-2R/STAT pathway, TGF-beta/Smad pathway, PI3K/Akt/mTOR axis, Notch signal pathway, IFN/IRF and IFN/nitric oxide axis, and epigenetic mechanisms. Some therapeutic agents on Foxp3 regulation were also reviewed. Points for attention in further study of Foxp3 transcription regulation, Such as the combinations/cross-talks, the bi-directional functions, and species specificity of these pathways, were discussed as well. (C) 2009 Wiley Periodicals, Inc. Med Res Rev, 29, No. 5. 742-766, 2009