Background: In coeliac disease ( CD) mucosa, the histological lesion is associated with marked infiltration of T helper cell type 1 (Th1) cells. However, the molecular mechanisms which regulate Th1 cell differentiation in CD mucosa are unknown. Aims: To analyse expression of transcription factors which control the Th1 cell commitment in CD. Patients: Duodenal mucosal samples were taken from untreated CD patients and normal controls. Methods: Interferon gamma (IFN-gamma) and interleukin (IL)-4 RNA expression was examined in T lamina propria lymphocytes by quantitative reverse transcription-polymerase chain reaction. T-bet and STAT-4, two Th1 promoting transcription factors, and STAT-6 and GATA-3, transcription factors which govern T helper cell type 2 (Th2) cell polarisation, were examined in duodenal biopsies by western blotting. The effect of gliadin and IFN-gamma on expression of T-bet was examined in an ex vivo culture of biopsies taken from normal and treated CD patients. Results: As expected, IFN-gamma but not IL-4 RNA transcripts were increased in the mucosa of CD patients in comparison with controls. CD mucosal samples consistently exhibited higher levels of T-bet than controls. However, no difference in active STAT-4 expression was seen between CD patients and controls, suggesting that Th1 polarisation was not induced by local IL-12. GATA-3 and STAT-6 were also low in both CD and control mucosa. In normal duodenal biopsies, IFN-gamma stimulated T-bet through a STAT-1 dependent mechanism. Challenge of treated CD but not control biopsies with gliadin enhanced T-bet and this effect was also inhibited by STAT-1 inhibition. Conclusions: This study shows that activation of STAT-1 by IFN-gamma promotes T-bet in CD mucosa.
Monteleone I., M.G. (2004). Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa. GUT, 53(8), 1090-1095.
|Tipologia:||Articolo su rivista|
|Citazione:||Monteleone I., M.G. (2004). Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa. GUT, 53(8), 1090-1095.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Nessuno|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1136/gut.2003.030551|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2004|
|Titolo:||Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa|
|Autori:||Monteleone I., Monteleone G., Del Vecchio Blanco G., Vavassori P., Cucchiara S., MacDonald T.T., Pallone F.|
|Appare nelle tipologie:||01 - Articolo su rivista|