Rani, A., Afzali, B., Kelly, A., Tewolde-Berhan, L., Hacket, M., Kanhere, A., Pedroza-Pacheco, I., Bowen, H., Jurcevic, S., Jenner, R., Cousins, D., Ragheb, J., Lavender, P. and John, S. 2011. IL-2 Regulates Expression of C-MAF in Human CD4 T Cells. Journal of Immunology. 187 (7), pp. 3721-3729. https://doi.org/10.4049/jimmunol.1002354
| Title | IL-2 Regulates Expression of C-MAF in Human CD4 T Cells |
|---|---|
| Type | Journal article |
| Authors | Rani, A., Afzali, B., Kelly, A., Tewolde-Berhan, L., Hacket, M., Kanhere, A., Pedroza-Pacheco, I., Bowen, H., Jurcevic, S., Jenner, R., Cousins, D., Ragheb, J., Lavender, P. and John, S. |
| Abstract | 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. |
| Journal | Journal of Immunology |
| Journal citation | 187 (7), pp. 3721-3729 |
| ISSN | 1550-6606 |
| Year | 2011 |
| Publisher | American Association of Immunologists |
| Accepted author manuscript | |
| Digital Object Identifier (DOI) | https://doi.org/10.4049/jimmunol.1002354 |
| Publication dates | |
| Published | 20 Sep 2011 |
| Funder | Wellcome Trust |
| MRC (Medical Research Council) |