PT  - JOURNAL ARTICLE
AU  - D Fina
AU  - M Sarra
AU  - R Caruso
AU  - G Del Vecchio Blanco
AU  - F Pallone
AU  - T T MacDonald
AU  - G Monteleone
TI  - Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease
AID  - 10.1136/gut.2007.129882
DP  - 2008 Jul 01
TA  - Gut
PG  - 887--892
VI  - 57
IP  - 7
4099  - http://gut.bmj.com/content/57/7/887.short
4100  - http://gut.bmj.com/content/57/7/887.full
SO  - Gut2008 Jul 01; 57
AB  - Background: In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon γ (IFNγ) and expressing the Th1-associated transcription factor, T-bet. However, the molecular mechanisms which regulate T-bet and promote the Th1 cell response are unknown.Objective: To examine whether interleukin 21 (IL21), a cytokine that regulates T cell activation, has a role in CD.Methods: Duodenal mucosal samples were taken from CD patients and normal controls. IL21 and T-bet were examined by real-time PCR and western blotting, and IFNγ was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated CD patients. Finally, the role of IL21 in controlling T-bet and IFNγ was also evaluated in cultures of biopsies taken from treated CD patients and cultured with a peptic–tryptic digest of gliadin (PT) in the presence or absence of a neutralising IL21 antibody.Results: Enhanced IL21 RNA and protein expression was seen in duodenal samples from untreated CD patients. Blockade of IL21 activity in biopsies of untreated CD patients reduced T-bet and IFNγ secretion. Stimulation of treated CD biopsies with PT enhanced IL21 expression, and neutralisation of IL21 largely prevented PT-driven T-bet and IFNγ induction.Conclusions: IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFNγ production.