Regulatory 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.
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.
|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.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|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:||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|