# Foxp3 Interacts With c-Rel to Mediate NF-$$\kappa$$B Repression

 Title: Foxp3 Interacts With c-Rel to Mediate NF-$$\kappa$$B Repression Author: Loizou, Louiza; Betz, Alexander G.; Andersen, Kristian G Note: Order does not necessarily reflect citation order of authors. Citation: Loizou, Louiza, Kristian G. Andersen, and Alexander G. Betz. 2011. Foxp3 interacts with c-Rel to mediate NF-$$\kappa$$B repression. PLoS ONE 6(4). Full Text & Related Files: 3072406.pdf (854.0Kb; PDF) Abstract: Expression of the lineage-specific DNA-binding factor Foxp3 controls the development and function of naturally occurring regulatory T cells. Foxp3 has been shown to interact with a multitude of transcriptional regulators including NFAT, NF-$$\kappa$$B (p65), Runx1 and ROR$$\lambda$$t, as well as the histone modification enzymes TIP60, HDAC7 and HDAC9. The sum of these interactions is believed to cause the change in the transcriptional program of regulatory T cells. Here we show that Foxp3 directly or as part of a multimeric complex engages with the NF-$$\kappa$$B component c-Rel. We demonstrate that the N-terminal region of Foxp3 is required for the binding of c-Rel, but not NFAT. Conversely, deletion of the forkhead domain causes a loss of interaction with NFAT, but not c-Rel. Our findings are of particular interest, as c-Rel is crucial for the induction of Foxp3 in regulatory T cells during thymic development, but has to be repressed in mature regulatory T cells to maintain their suppressive phenotype. Published Version: doi://10.1371/journal.pone.0018670 Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072406/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11213364 Downloads of this work: