Background: In celiac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon (IFN)-[gamma] 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 (IL-)21, a cytokine that regulates T cell activation, has a role in CD. Setting: Duodenal mucosal samples were taken from CD patients and normal controls. IL-21 and T-bet were examined by real-time PCR and Western blotting, and IFN-[gamma]was assessed by real-time PCR and ELISA. The effect of blockade of endogenous IL-21 on the expression of T-bet was examined in an ex vivo culture of biopsies taken from untreated CD patients. Finally, the role of IL-21 in controlling T-bet and IFN-[gamma] 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 neutralizing IL-21 antibody. Results: Enhanced IL-21 RNA and protein expression was seen in duodenal samples from untreated CD patients. Blockade of IL-21 activity in biopsies of untreated CD patients reduced T-bet and IFN-[gamma] secretion. Stimulation of treated CD biopsies with PT-gliadin enhanced IL-21 expression, and neutralization of IL-21 largely prevented PT-driven T-bet and IFN-[gamma] induction. Conclusions: IL-21 is over-produced in the mucosa of CD patients, where it helps sustain T-bet expression and IFN-[gamma] production.
- celiac disease