IL-2 Regulates Expression of C-MAF in Human CD4 T Cells
| العنوان: | IL-2 Regulates Expression of C-MAF in Human CD4 T Cells |
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| المؤلفون: | Susan D. John, Audrey Kelly, Aditi Kanhere, Richard G. Jenner, Lemlem Tewolde-Berhan, Mark Hackett, Holly Bowen, Aradhana Rani, Jack A. Ragheb, Isabela Pedroza-Pacheco, Paul Lavender, Behdad Afzali, David J. Cousins, Stipo Jurcevic |
| المصدر: | The Journal of Immunology. 187:3721-3729 |
| بيانات النشر: | The American Association of Immunologists, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Interleukin 2, ZAP70, Cellular differentiation, Immunology, Biology, Molecular biology, Chromatin, Interleukin 21, medicine, Immunology and Allergy, Cytotoxic T cell, IL-2 receptor, Interleukin 4, medicine.drug |
| الوصف: | Blockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2 responses in human T cells. Recent murine studies have shown that IL-2 also plays a significant role in regulating Th2 cell differentiation by activated STAT5. To explore the role of activated STAT5 in the Th2 differentiation of primary human T cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression. Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to specific sites in the C-MAF promoter. These sites corresponded to regions enriched for markers of chromatin architectural features in both resting CD4 and differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T cells with or without prior TCR stimulation. TCR-induced C-MAF expression was significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333. Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR-activated T cells, suggesting functional cooperation between these cytokines. Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus, our findings demonstrate the importance of IL-2 in Th2 differentiation in human T cells and support the notion that IL-2R–directed therapies may have utility in the treatment of allergic disorders. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::788c53e4b55115684238bc0e4ce2f3c1Test https://doi.org/10.4049/jimmunol.1002354Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........788c53e4b55115684238bc0e4ce2f3c1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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