Coeliac disease

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

D Fina¹, M Sarra¹, R Caruso¹, G Del Vecchio Blanco¹, F Pallone¹, T T MacDonald², G Monteleone¹

¹ Dipartimento di Medicina Interna e Centro di Eccellenza per lo studio delle malattie complesse e multifattoriali, Universitè Tor Vergata, Rome, Italy
² Institute of Cell and Molecular Science, Bart’s and the London School of Medicine and Dentistry, London, UK

Professor G Monteleone, Dipartimento di Medicina Interna, Universitè Tor Vergata, Via Montpellier, 1, 00133 Rome, Italy; Gi.Monteleone{at}Med.uniroma2.it

Background: In coeliac disease (CD), the upper bowel lesion is associated with a marked infiltration of the mucosa with Th1 cells secreting interferon (IFN) 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 IFN 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 IFN 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 IFN secretion. Stimulation of treated CD biopsies with PT enhanced IL21 expression, and neutralisation of IL21 largely prevented PT-driven T-bet and IFN induction.

Conclusions: IL21 is overproduced in the mucosa of CD patients, where it helps sustain T-bet expression and IFN production.

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