دورية أكاديمية
Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression.
| العنوان: | Inhibition of the JAK/STAT Signaling Pathway in Regulatory T Cells Reveals a Very Dynamic Regulation of Foxp3 Expression. |
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| المؤلفون: | Jérémie D Goldstein, Aude Burlion, Bruno Zaragoza, Kélhia Sendeyo, Julia K Polansky, Jochen Huehn, Eliane Piaggio, Benoit L Salomon, Gilles Marodon |
| المصدر: | PLoS ONE, Vol 11, Iss 4, p e0153682 (2016) |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | The 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1932-6203 |
| Relation: | http://europepmc.org/articles/PMC4831811?pdf=render; https://doaj.org/toc/1932-6203 |
| DOI: | 10.1371/journal.pone.0153682 |
| URL الوصول: | https://doaj.org/article/61e67450ddb84f7a9caa313f101a5655 |
| رقم الأكسشن: | edsdoj.61e67450ddb84f7a9caa313f101a5655 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0153682 |