Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression.
Goldstein et al.PDF
Open Access publication
Erratum to Goldstein et al
supporting figure S1
supporting figure S2
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
AuthorsGoldstein, Jérémie D
Polansky, Julia K
Salomon, Benoit L
MetadataShow full item record
AbstractThe IL-2/JAK3/STAT-5 signaling pathway is involved on the initiation and maintenance of the transcription factor Foxp3 in regulatory T cells (Treg) and has been associated with demethylation of the intronic Conserved Non Coding Sequence-2 (CNS2). However, the role of the JAK/STAT pathway in controlling Foxp3 in the short term has been poorly investigated. Using two different JAK/STAT pharmacological inhibitors, we observed a detectable loss of Foxp3 after 10 min. of treatment that affected 70% of the cells after one hour. Using cycloheximide, a general inhibitor of mRNA translation, we determined that Foxp3, but not CD25, has a high turnover in IL-2 stimulated Treg. This reduction was correlated with a rapid reduction of Foxp3 mRNA. This loss of Foxp3 was associated with a loss in STAT-5 binding to the CNS2, which however remains demethylated. Consequently, Foxp3 expression returns to normal level upon restoration of basal JAK/STAT signaling in vivo. Reduced expression of several genes defining Treg identity was also observed upon treatment. Thus, our results demonstrate that Foxp3 has a rapid turn over in Treg partly controlled at the transcriptional level by the JAK/STAT pathway.
CitationInhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression. 2016, 11 (4):e0153682 PLoS ONE
AffiliationHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- TGF-β-mediated Foxp3 gene expression is cooperatively regulated by Stat5, Creb, and AP-1 through CNS2.
- Authors: Ogawa C, Tone Y, Tsuda M, Peter C, Waldmann H, Tone M
- Issue date: 2014 Jan 1
- Control of the inheritance of regulatory T cell identity by a cis element in the Foxp3 locus.
- Authors: Feng Y, Arvey A, Chinen T, van der Veeken J, Gasteiger G, Rudensky AY
- Issue date: 2014 Aug 14
- Interplay between mTOR and STAT5 signaling modulates the balance between regulatory and effective T cells.
- Authors: Shan J, Feng L, Sun G, Chen P, Zhou Y, Xia M, Li H, Li Y
- Issue date: 2015 Apr
- Upregulation of Foxp3 expression in mouse and human Treg is IL-2/STAT5 dependent: implications for the NOD STAT5B mutation in diabetes pathogenesis.
- Authors: Murawski MR, Litherland SA, Clare-Salzler MJ, Davoodi-Semiromi A
- Issue date: 2006 Oct
- DNA methylation controls Foxp3 gene expression.
- Authors: Polansky JK, Kretschmer K, Freyer J, Floess S, Garbe A, Baron U, Olek S, Hamann A, von Boehmer H, Huehn J
- Issue date: 2008 Jun