Increased Act1/IL-17R expression in Hirschsprung's disease

Area of Science:

• Gastroenterology and Hepatology
• Immunology
• Pediatric Surgery

Background:

• Hirschsprung's disease-associated enterocolitis (HAEC) is a severe complication of Hirschsprung's disease (HSCR), leading to significant morbidity and mortality.
• Altered intestinal epithelial barrier function is a key factor in HAEC development.
• Interleukin-17 (IL-17) signaling, mediated by the Act1 adaptor protein and IL-17 receptor (IL-17R), is crucial in inflammatory responses.

Purpose of the Study:

• To investigate the expression levels of Act1 and IL-17R in patients with HSCR.
• To determine if Act1 and IL-17R expression is upregulated in the colonic tissue of HSCR patients compared to controls.

Main Methods:

• Expression analysis of Act1 and IL-17R was performed on ganglionic and aganglionic bowel specimens from HSCR patients (n=10) and controls (n=10).
• Quantitative real-time PCR (qPCR) and Western blotting were used to assess protein and gene expression levels.
• Confocal immunofluorescence microscopy was employed to visualize the localization and expression of Act1 and IL-17R in colonic epithelium.

Main Results:

• Act1 and IL-17R were strongly expressed in both ganglionic and aganglionic colon segments of HSCR patients.
• A statistically significant increase (p < 0.05) in Act1 and IL-17R expression was observed in HSCR specimens compared to controls.
• Confocal microscopy confirmed markedly elevated expression of Act1 and IL-17R within the colonic epithelium of HSCR patients.

Conclusions:

• This study provides the first report of Act1 expression in the human colon.
• The elevated expression of Act1 and IL-17R in the HSCR bowel suggests a potential role in heightened IL-17-mediated inflammation.
• Increased Act1/IL-17R signaling may contribute to the pathogenesis of HAEC in patients with Hirschsprung's disease.