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dc.contributor.authorGoldstein, Jérémie D
dc.contributor.authorBurlion, Aude
dc.contributor.authorZaragoza, Bruno
dc.contributor.authorSendeyo, Kélhia
dc.contributor.authorPolansky, Julia K
dc.contributor.authorHuehn, Jochen
dc.contributor.authorPiaggio, Eliane
dc.contributor.authorSalomon, Benoit L
dc.contributor.authorMarodon, Gilles
dc.date.accessioned2016-09-13T07:57:50Z
dc.date.available2016-09-13T07:57:50Z
dc.date.issued2016
dc.identifier.citationInhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression. 2016, 11 (4):e0153682 PLoS ONEen
dc.identifier.issn1932-6203
dc.identifier.pmid27077371
dc.identifier.doi10.1371/journal.pone.0153682
dc.identifier.urihttp://hdl.handle.net/10033/620051
dc.description.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.
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshDNA Methylationen
dc.subject.meshForkhead Transcription Factorsen
dc.subject.meshGene Expression Regulationen
dc.subject.meshHumansen
dc.subject.meshIntronsen
dc.subject.meshJanus Kinase 3en
dc.subject.meshMiceen
dc.subject.meshProtein Kinase Inhibitorsen
dc.subject.meshRNA, Messengeren
dc.subject.meshSTAT5 Transcription Factoren
dc.subject.meshSignal Transductionen
dc.subject.meshT-Lymphocytes, Regulatoryen
dc.titleInhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalPloS oneen
refterms.dateFOA2018-06-13T01:10:28Z
html.description.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.


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