In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease

Abstract

CONCLUSIONS:In potential CD, IL-21 is less expressed than in active CD; however, IL-21-producing cells are present and prone to respond after specifi c stimuli. This suggests a key role of IL-21 in the progression of mucosal damage in CD.SUPPLEMENTARY MATERIAL is linked to the online version of the paper at

The intestinal expansion of TCRγδ+ and disappearance of IL4+ T cells suggest their involvement in the evolution from potential to overt celiac disease

“…Although a reduced mucosal infiltration of IL21‐positive cells in potential‐CD has been reported, we have previously demonstrated that in the gut mucosa of this peculiar group of CD patients, IL‐21‐producing cells are present and prone to respond after strong stimuli, as the PMA/ion mitogen or gliadin in organ culture. These results, obtained in a different cohort of children with potential‐CD, confirm and corroborate our previous findings . Interestingly, the potential‐ and overt‐CD were characterized by two distinct subsets of Th1 cells.…”

“…IL21 is a key mediator in the pathogenesis of villous atrophy as demonstrated by several studies in both adult and childhood CD . In particular, CD4 + T cells releasing IL21 were found increased in inflamed mucosa of overt‐CD patients and able to stimulate the tissue production of IFN‐γ and T‐bet (Th1 transcription factor) .…”

“…Potential‐CD is a condition defined by the presence of HLA DQ2/DQ8 risk alleles, positive CD‐associated serological markers but a mucosa with normal architecture . Recent findings have demonstrated the presence in the gut of subjects with potential‐CD of inflammatory T cells reactive to gluten peptides , concomitantly with the existence of regulatory mechanisms that counteract the activation of inflammatory pathways destructive of mucosal epithelium. Interestingly, another study has instead reported the lack of NK‐mediated cytotoxic pattern in the gut of this peculiar group of patients .…”

“…IFN‐γ is the dominant one, but also IL21 is markedly expressed in celiac mucosa, being specifically released by intestinal T cells upon gluten exposure . The high expression of IL21 found in the intestinal mucosa of both pediatric and adult patients with overt‐CD suggests an important function of this inflammatory cytokine in the anti‐gluten immune response. On the other side, although it is well established that CD4 + Th17 cells producing IL17 play a role in chronic intestinal disorders , to date, conflicting data have been reported on their function in gluten‐triggered mucosa damage in CD .…”

Diagnosing Celiac Disease: Towards Wide-Scale Screening and Serology-Based Criteria?

“…Nevertheless, many such individuals are asymptomatic and do not develop duodenal lesions even during a long-term follow-up [49, 105–107]. It is essential to learn more about the natural history of early developing celiac disease in order to discern cases that would truly benefit from early diagnosis [108].…”