Article Text

PDF
Interleukin 21 contributes to the mucosal T helper cell type 1 response in coeliac disease
  1. D Fina1,
  2. M Sarra1,
  3. R Caruso1,
  4. G Del Vecchio Blanco1,
  5. F Pallone1,
  6. T T MacDonald2,
  7. G Monteleone1
  1. 1
    Dipartimento di Medicina Interna e Centro di Eccellenza per lo studio delle malattie complesse e multifattoriali, Universitè Tor Vergata, Rome, Italy
  2. 2
    Institute of Cell and Molecular Science, Bart’s and the London School of Medicine and Dentistry, London, UK
  1. Professor G Monteleone, Dipartimento di Medicina Interna, Universitè Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy; Gi.Monteleone{at}Med.uniroma2.it

Abstract

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.

Statistics from Altmetric.com

Footnotes

  • Competing interests: None.

  • Ethics approval: This study received approval from the University Tor Vegata of Rome ethical committee.

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles