The cytokine interleukin 21: a new player in coeliac disease?

In this issue of Gut ,1 Fina et al demonstrate that interleukin 21 (IL21) expression is increased in the intestinal mucosa of patients with active coeliac disease (CD) but not that of treated patients ( see page 887 ). The authors show that IL21 is produced by CD4+ lamina propria T cells, a finding consistent with previous work indicating that this cytokine is exclusively produced by CD4+ T cells. Using a neutralising anti-IL21 antibody, they observed that blocking IL21 activity reduced the increase in interferon γ mRNA induced by gliadin digests in intestinal organ cultures from treated CD patients. Since the anti-IL21 antibody also reduced the induction of mRNA for T-bet, the transcription factor that controls the differentiation of interferon γ-producing CD4+ T lymphocytes (so-called T helper cell type 1 or Th1 lymphocytes), the authors conclude that IL21 is an important contributor to the mucosal Th1 proinflammatory response.1 The mucosal Th1 response in CD is generally ascribed to lamina propria CD4+ T cells that recognise gluten peptides presented by the human leucocyte antigen (HLA)-DQ2/8 molecules at the surface of mucosal dendritic cells. This response accounts for the interplay between the major genetic risk factor, the MHC (major histocompatibility complex) class II genes encoding the HLA-DQ2/8 molecules, and the triggering environmental factor gluten, and is considered instrumental in the pathogenesis of CD enteropathy.2 These results are of particular interest following the first genome-wide association study recently carried out in CD by van Heel et al .3 The latter study has indeed provided convincing evidence that the chromosomal 4q27 region harbouring the genes encoding the IL2 and IL21 cytokines might be involved in CD. In this study based on the use of single-nucleotide polymorphisms (SNPs), several variants were highly significant when analysed in three distinct populations of UK, Dutch and …