TITLE

Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease

AUTHOR(S)
Fina, D.; Sarra, M.; Caruso, R.; Del Vecchio Blanco, G.; Pallone, F.; MacDonald, T. T.; Monteleone, G.
PUB. DATE
July 2008
SOURCE
Gut;Jul2008, Vol. 57 Issue 7, p887
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Thi 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 lL21 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.
ACCESSION #
32894051

 

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