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Updated: May 5, 2026

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes
Published on: September 26, 2013
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.
Objective:
The aim was to investigate the mucosal activation of a broad range of genes associated with the T-helper 17 cell (Th17) signaling pathway in children at different stages of celiac disease (CD), including children with increased risk for CD and children with untreated and gluten-free diet (GFD)-treated CD.
Material And Methods:
Small intestinal biopsies were taken from children with untreated and GFD-treated CD, transglutaminase antibody (TGA)-positive children with potential CD, and reference children. Real-time polymerase chain reaction (PCR) arrays were used to study the gene expression pattern of Th17-related genes, and quantitative PCR was used to study the interleukin (IL)-17A expression.
Results:
The mucosal expression of CD8A was elevated at all stages of CD. Children with untreated CD had diminished levels of IL-17RE, IL-23R, RORc, STAT6, CCL22, NFATC2, IL-18, CD4, CD247, and matrix metalloproteinase (MMP)9 but had elevated levels of MMP3, IL-17, interferon-γ (IFN-γ) and CD8A, compared to references. The majority of the aforementioned genes, being differentially expressed in untreated CD, displayed similar expression in GFD-treated children and references. Children with untreated and GFD-treated CD had elevated expression of IFN-γ but had reduced expression of CD247. Interestingly, children with potential CD displayed reduced FOXP3, IL-21, and IL-17A levels.
Conclusion:
Mucosal upregulation of Th17 immunity occurs at the late stage of disease and is downregulated with dietary treatment, thus indicating that IL-17 immunity is not a fundamental feature of CD as Th1 immunity, which is not fully downregulated by GFD.
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