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Interleukin-21 Contributes To The Mucosal T Helper Cell Type 1 Response In Celiac Disease
  1. Daniele Fina
  1. University Tor Vergata of Rome, Italy
    1. Massimiliano Sarra
    1. University Tor Vergata of Rome, Italy
      1. Roberta Caruso
      1. University Tor Vergata of Rome, Italy
        1. Giovanna Del Vecchio Blanco
        1. University Tor Vergata of Rome, Italy
          1. Francesco Pallone
          1. University Tor Vergata of Rome, Italy
            1. Thomas T MacDonald
            1. Institute of Cell and Molecular Science, Bart’s and the London School of Medicine and Dentistry, Lon, United Kingdom
              1. Giovanni Monteleone (gi.monteleone{at}med.uniroma2.it)
              1. University Tor Vergata of Rome, Italy

                Abstract

                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.

                • IL-21
                • T-bet
                • celiac disease

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