RT Journal Article
SR Electronic
T1 Regulation of the T helper cell type 1 transcription factor T-bet in coeliac disease mucosa
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 1090
OP 1095
DO 10.1136/gut.2003.030551
VO 53
IS 8
A1 I Monteleone
A1 G Monteleone
A1 G Del Vecchio Blanco
A1 P Vavassori
A1 S Cucchiara
A1 T T MacDonald
A1 F Pallone
YR 2004
UL http://gut.bmj.com/content/53/8/1090.abstract
AB 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 γ (IFN-γ) 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-γ 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-γ 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-γ 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-γ promotes T-bet in CD mucosa.