Altered expression of IL36γ and IL36 receptor (IL1RL2) in the colon of patients with Hirschsprung's disease.

Abstract

Hirschsprung's disease associated enterocolitis (HAEC) is the most common cause of morbidity and mortality in Hirschsprung's disease (HSCR). Altered intestinal epithelial barrier function and abnormal microbiota are implicated in the pathogenesis of HAEC. IL-36γ, a member of the IL-1 superfamily, is involved in host defense and contributes to proinflammatory responses and development of inflammatory diseases. The IL36 receptor (IL1RL2) is an important mediator molecule in the inflammatory response. Animal data suggests that IL1RL2 is involved in mucosal healing. We designed this study to investigate the hypothesis that the IL-36γ axis is altered in HSCR. We investigated IL-36γ and IL1RL2 expression in ganglionic and aganglionic bowel of HSCR patients (n=10) and controls (n=10). qPCR, Western blotting and confocal immunofluorescence were performed. qPCR and Western blot analysis revealed that IL-36γ is strongly expressed in the aganglionic and ganglionic colon of patients with HSCR. ILR1L2 expression was significantly decreased in HSCR specimens compared to controls (p<0.05). Confocal microscopy revealed a markedly increased expression of IL36γ in the colonic epithelium of patients with HSCR compared to controls. IL1RL2 was localized in the colonic epithelium and showed a markedly decreased expression in all HSCR specimens. To our knowledge, we report for the first time the expression of IL36γ and ILRL2 in the colon of patients with HSCR. The increased expression of IL36γ and the markedly decreased expression of IL1RL2 in the aganglionic and ganglionic bowel in HSCR may result in an increased inflammatory response and altered mucosal response healing leading to the susceptibility to develop HAEC.