%0 Journal Article
%T The Treg-Specific Demethylated Region Stabilizes Foxp3 Expression Independently of NF-百B Signaling
%A Lisa Schreiber
%A Beate Pietzsch
%A Stefan Floess
%A Carla Farah
%A Lothar Jˋnsch
%A Ingo Schmitz
%A Jochen Huehn
%J PLOS ONE
%D 2014
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0088318
%X Regulatory T cells (Tregs) obtain immunosuppressive capacity by the upregulation of forkhead box protein 3 (Foxp3), and persistent expression of this transcription factor is required to maintain their immune regulatory function and ensure immune homeostasis. Stable Foxp3 expression is achieved through epigenetic modification of the Treg-specific demethylated region (TSDR), an evolutionarily conserved non-coding element within the Foxp3 gene locus. Here, we present molecular data suggesting that TSDR enhancer activity is restricted to T cells and cannot be induced in other immune cells such as macrophages or B cells. Since NF-百B signaling has been reported to be instrumental to induce Foxp3 expression during Treg development, we analyzed how NF-百B factors are involved in the molecular regulation of the TSDR. Unexpectedly, we neither observed transcriptional activity of a previously postulated NF-百B binding site within the TSDR nor did the entire TSDR show any transcriptional responsiveness to NF-百B activation at all. Finally, the NF-百B subunit c-Rel revealed to be dispensable for epigenetic imprinting of sustained Foxp3 expression by TSDR demethylation. In conclusion, we show that NF-百B signaling is not substantially involved in TSDR-mediated stabilization of Foxp3 expression in Tregs.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0088318