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EnglishRegulatory T (T-reg) cells play a key role in the maintenance of the immune system homeostasis. T-reg cells can be generated in the periphery under control of TGF-beta, a cytokine involved in the negative control of the immune system. However, TGF-beta cooperates with IL-6 in the generation of Th17 cells, a novel class of effector cells involved in numerous inflammatory diseases, including colitis. Therefore, TGF-beta emerges as a mediator of both anti-inflammatory and pro-inflammatory processes, depending on the local cytokine milieu. Here we demonstrate that IL-21, a type-1 cytokine produced by T cells and involved in the pathogenesis of immune-mediated diseases, prevents the TGF-beta-dependent expression of FoxP3, the master regulator of T-reg cell commitment, and the induction of suppressive capacity in naive CD4(+) T cells, while promoting the differentiation of Th17 cells. In vivo, CD4(+) naive T cells activated in the presence of TGF-beta and IL-21 failed to suppress colitis while inducing an inflammatory response characterized by high levels of IL-17 and ROR gamma t, the transcription factor expressed by Th17 cells. Therefore, IL-21 emerges as a key modulator of TGF-beta signaling, leading to the reciprocal differentiation of Treg and Th17 cells.
| Tipologia: | Articolo su rivista |
| Citazione: | Fantini M.C., R.A. (2007). IL-21 regulates experimental colitis by modulating the balance between T-reg and Th17 cells. EUROPEAN JOURNAL OF IMMUNOLOGY, 37(11), 3155-3163. |
| Lingua: | English |
| Settore Scientifico Disciplinare: | Settore MED/12 - Gastroenterologia |
| Revisione (peer review): | Sì, ma tipo non specificato |
| Tipo: | Articolo |
| Rilevanza: | Rilevanza internazionale |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1002/eji.200737766 |
| Stato di pubblicazione: | Pubblicato |
| Data di pubblicazione: | 2007 |
| Titolo: | IL-21 regulates experimental colitis by modulating the balance between T-reg and Th17 cells |
| Autori: | |
| Autori: | Fantini M.C., Rizzo A., Fina D., Caruso R., Becker C., Neurath M.F., MacDonald T.T., Pallone F., Monteleone G. |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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