Background & Aims: T-helper (Th)1 cells play a central role in the pathogenesis of tissue damage in Crohn's disease (CD). Interleukin (IL)-12/STAT4 signaling promotes Th1 cell commitment in CD, but other cytokines are needed to maintain activated Th:1 cells in the mucosa. In this study, we examined the expression and role of IL-21, a T-cell-derived cytokine of the IL-2 family; in tissues and cells isolated from patients with inflammatory bowel disease. Methods: IL-21 was examined by Western blotting in whole mucosa and lamina propria mononuclear cells (LP-MCs) from patients with CD, ulcerative colitis (UC), and controls. We also examined the effects of exogenous IL-12 on IL-21 production, as well as the effects of blocking IL-21 with an IL-21-receptor Ig fusion protein. Interferon (IFN)-gamma was measured in the culture supernatants by enzyme-linked immunosorbent assay, and phosphorylated STAT4 and T-bet were examined by Western blotting. Results: IL-21 was detected in all samples, but its expression was higher at the site of disease in CD in comparison with UC and controls. Enhanced IL-21 was seen in both ileal and colonic CD and in fibrostenosing and nonfibrostenosing disease. IL-12 enhanced IL-21 in normal lamina propria lymphocytes through an IFN-gamma-independent mechanism, and blocking IL-12 in CD LP-MCs decreased anti-CD3-stimulated IL-21 expression. Neutralization of IL-21 in CD LPMC cultures decreased phosphorylated STAT4 and T-bet expression, thereby inhibiting IFN-gamma production. Conclusions: Our data suggest that IL-21 contributes to the ongoing Th1 mucosal response in CD.
Monteleone, G., Monteleone, I., Fina, D., Vavassori, P., Del Vecchio Blanco, G., Caruso, R., et al. (2005). Interleukin-21 enhances T-helper cell type 1 signaling and interferon-gamma production in Crohn's disease. GASTROENTEROLOGY, 128(3), 687-694.
|Tipologia:||Articolo su rivista|
|Citazione:||Monteleone, G., Monteleone, I., Fina, D., Vavassori, P., Del Vecchio Blanco, G., Caruso, R., et al. (2005). Interleukin-21 enhances T-helper cell type 1 signaling and interferon-gamma production in Crohn's disease. GASTROENTEROLOGY, 128(3), 687-694.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1053/j.gastro.2004.12.042|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2005|
|Titolo:||Interleukin-21 enhances T-helper cell type 1 signaling and interferon-gamma production in Crohn's disease|
|Autori:||Monteleone, G; Monteleone, I; Fina, D; Vavassori, P; Del Vecchio Blanco, G; Caruso, R; Tersigni, R; Alessandroni, L; Biancone, L; Naccari, GC; Macdonald,TT; Pallone, F|
|Appare nelle tipologie:||01 - Articolo su rivista|