Expression pattern of T-helper 17 cell signaling pathway and mucosal inflammation in celiac disease

Anne I Lahdenperä1, Karin Fälth-Magnusson, Lotta Högberg

  • 1Department of Clinical and Experimental Medicine, Division of Paediatrics, Faculty of Health Sciences, Linköping University , Linköping , Sweden.

Insights

T-helper 17 (Th17) cell activation in celiac disease (CD) is a late-stage event, downregulated by a gluten-free diet (GFD). This suggests Th17 immunity is not a core feature of CD, unlike Th1 immunity.

Area of Science:

  • Immunology
  • Gastroenterology
  • Pediatrics

Background:

  • Celiac disease (CD) involves complex immune responses.
  • T-helper 17 (Th17) cells play a role in various autoimmune conditions.
  • Understanding Th17 pathway gene expression in pediatric CD is crucial.

Purpose of the Study:

  • To investigate mucosal Th17 signaling pathway gene activation in children across different stages of celiac disease.
  • To compare gene expression in children at risk, with untreated CD, and on a gluten-free diet (GFD).

Main Methods:

  • Small intestinal biopsies from pediatric cohorts (untreated CD, GFD-treated CD, potential CD, controls) were analyzed.
  • Real-time PCR arrays assessed Th17-related gene expression.
  • Quantitative PCR measured interleukin (IL)-17A expression.

Main Results:

  • Elevated CD8A expression was observed at all CD stages.
  • Untreated CD showed decreased IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and MMP9, but increased MMP3, IL-17, IFN-γ, and CD8A compared to controls.
  • GFD-treated CD largely mirrored control gene expression, except for elevated IFN-γ and reduced CD247.
  • Potential CD cases exhibited reduced FOXP3, IL-21, and IL-17A.

Conclusions:

  • Mucosal Th17 immunity upregulation occurs late in celiac disease progression.
  • Dietary treatment with a gluten-free diet downregulates Th17 pathway activation.
  • IL-17 immunity is not a fundamental characteristic of CD, unlike Th1 immunity, which persists despite GFD.
Abstract

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