Mucosal expression of Toll-like receptors (TLR2, TLR3 and TLR4) in children with coeliac disease

Background and aim: Besides the central role of the adaptive immunity, innate immune responses also play an important role in the development of coeliac disease. Recently it has been found that rod-shaped bacteria are frequently associated with the mucosa of coeliac disease patients but not with controls. Bacterial products are recognized by pattern recognition receptors (PRRs) like Toll-like receptors (TLRs), which are key regulators of the innate immune system. After ligand binding these receptors trigger the release of proinflammatory or chemotactic cytokines and chemokines, thus lowering the thereshold for the activation of gluten reactive CD4+T cells in the lamina propria. The aim of this study was to characterise the expression of TLR2, TLR3 and TLR4 in intestinal biopsy samples from children with coeliac disease and controls.

Methods: Duodenal biopsy samples were collected from 16 children with untreated coeliac disease [meadian age (range): 9 (4–15) yr] and 10 controls [10 (4–15) yr]. One sample from each patient was used for routine diagnostic purposes. The TLR2, TLR3 and TLR4 gene expression were evaluated by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR).

Results: All coeliac patients had endomysium IgA positivity and subtotal villous atrophy in the small intestinal mucosa. All controls had normal histological finding. An eightfold increase of mRNA for TLR2 and fourfold for TLR4 were detected in the coeliac biopsy samples compared to controls (p<0.05 for both). The expression of TLR3 gene was not significantly different.

Conclusions: Increased TLR2 and TLR4 genes expression was found in children with coeliac disease. These data suggest that coeliac disease is associated with increased TLR expression in the intestinal mucosa, implying that alterations of innate immune system may contribute to the pathogenesis of this disorder.