| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
|
|
|
|
|||||||||||||
|
|
|||||||||||||||
COELIAC DISEASE |
1 Dipartimento di Medicina Interna e Centro di Eccellenza per lo studio delle malattie complesse e multifattoriali, Università Tor Vergata, Rome, Italy
2 Pediatric Unit, University "La Sapienza", Rome, Italy
3 Division of Infection, Inflammation, and Repair, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK
Correspondence to:
Correspondence to:
Dr G Monteleone
Dipartimento di Medicina Interna, Università Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy; Gi.Monteleone{at}Med.uniroma2.it
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 
(IFN-) 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- 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- 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- 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- promotes T-bet in CD mucosa.
Abbreviations: CD, coeliac disease; Th1, T helper cell type 1; Th2, T helper cell type 2; IFN, interferon; IL, interleukin; T-LPL, lamina propria T lymphocytes; EMA, antiendomysial antibodies; DMSO, dimethylsulphoxide; PT, peptic-tryptic digest of gliadin; LPMC, lamina propria mononuclear cells
Keywords: coeliac disease; T-bet; STAT-1
Relevant Article
Gut 2004 53: 1065-1067.
This article has been cited by other articles:
|
|
 |
|
  D Fina, M Sarra, R Caruso, G Del Vecchio Blanco, F Pallone, T T MacDonald, and G Monteleone Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease Gut, July 1, 2008; 57(7): 887 - 892. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A Di Sabatino, K M Pickard, D Rampton, L Kruidenier, L Rovedatti, N A B Leakey, G R Corazza, G Monteleone, and T T MacDonald Blockade of transforming growth factor {beta} upregulates T-box transcription factor T-bet, and increases T helper cell type 1 cytokine and matrix metalloproteinase-3 production in the human gut mucosa Gut, May 1, 2008; 57(5): 605 - 612. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Silano, R. Di Benedetto, F. Maialetti, A. De Vincenzi, R. Calcaterra, A. Trecca, and M. De Vincenzi A 10-residue peptide from durum wheat promotes a shift from a Th1-type response toward a Th2-type response in celiac disease Am. J. Clinical Nutrition, February 1, 2008; 87(2): 415 - 423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Inman, K. Kawana, D. Schust, R. Lininger, and S. Young Cyclic Regulation of T-Bet and GATA-3 in Human Endometrium Reproductive Sciences, January 1, 2008; 15(1): 83 - 90. [Abstract] [PDF]
|
|
|
|
 |
|
 C. G. Rizzello, M. De Angelis, R. Di Cagno, A. Camarca, M. Silano, I. Losito, M. De Vincenzi, M. D. De Bari, F. Palmisano, F. Maurano, et al. Highly Efficient Gluten Degradation by Lactobacilli and Fungal Proteases during Food Processing: New Perspectives for Celiac Disease Appl. Envir. Microbiol., July 15, 2007; 73(14): 4499 - 4507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B C Dickson, C J Streutker, and R Chetty Coeliac disease: an update for pathologists. J. Clin. Pathol., October 1, 2006; 59(10): 1008 - 1016. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS | REGISTER |
