Related Experiment Video
Updated: Jun 8, 2026
Chronic Salmonella Infection Induced Intestinal Fibrosis
Published on: September 22, 2019
Strong overexpression of CXCR3 axis components in childhood inflammatory bowel disease
Sebastian Schroepf1, Roland Kappler, Stephan Brand
1Department of Pediatric Surgery, Research Laboratories, University of Munich, Munich, Germany.
Insights
The CXCR3 axis is overexpressed in active Inflammatory Bowel Disease (IBD), indicating its role in disease development. A specific CXCL11 gene variant (rs6817952 A) is linked to increased risk in pediatric Crohn's disease and all ages with ulcerative colitis.
Area of Science:
- Gastroenterology
- Immunology
- Genetics
Background:
- Inflammatory Bowel Disease (IBD) is a complex polygenetic disorder.
- Previous research linked a CXCL9 gene variant to pediatric Crohn's disease.
- CXCL9, CXCL10, and CXCL11 are ligands for the CXCR3 receptor.
Purpose of the Study:
- Investigate the colonic transcriptional activity of the CXCR3 axis in IBD.
- Perform Single Nucleotide Polymorphism (SNP) genotyping of a CXCL11 polymorphism in IBD patients.
- Analyze the association of the CXCL11 rs6817952 variant with IBD risk across pediatric and adult populations.
Main Methods:
- Real-time PCR was used to analyze mRNA expression of CXCR3, CXCL9, CXCL10, CXCL11, and IL8 in colonic biopsies.
- TaqMan SNP genotyping assay determined the CXCL11 rs6817952 nucleotide substitution.
- The study included 501 German individuals with IBD (pediatric and adult) and 231 controls.
Main Results:
- CXCR3 axis genes were significantly overexpressed in inflamed colonic tissue of pediatric Crohn's disease (CD) and ulcerative colitis (UC) patients.
- The rs6817952 genotype variants were more prevalent in pediatric CD patients compared to controls.
- Carriers of rs6817952 variants had an increased risk for UC across all age groups.
Conclusions:
- The CXCR3 axis is significantly overexpressed in active IBD, suggesting a role in disease pathogenesis.
- The rs6817952 A variant acts as a risk allele for pediatric CD and for UC in all age groups.
- Further therapeutic studies are warranted to explore CXCR3 blockade for modulating intestinal inflammation in IBD.
Background:
Inflammatory bowel disease (IBD) is a polygenetic disorder. Our group previously showed that a variant within the CXCL9 gene is associated with pediatric Crohn's disease. As CXCL9, CXCL10, and CXCL11 are the 3 ligands to the receptor CXCR3, the aim of this study was to investigate the colonic transcriptional activity of the CXCR3 axis and to perform SNP genotyping of a CXCL11 polymorphism in a large pediatric and adult IBD cohort.
Methods:
mRNA expression of CXCR3, CXCL9, CXCL10, CXCL11, and IL8 was analyzed in colonic biopsies using real-time PCR. CXCL11 rs6817952 nucleotide substitution was determined in 501 German individuals with IBD (336 CD, 165 UC) including 258 children and 243 adults as well as in 231 controls by a TaqMan SNP genotyping assay.
Results:
CXCR3 axis genes were significantly overexpressed in inflamed colonic tissue of pediatric CD and UC patients. The prevalence of hetero- and homozygous variants of the rs6817952 genotype was higher in pediatric but not in adult CD patients compared with that in controls (P = 0.04). Moreover, carriers of the hetero- and homozygous genotype variants of rs6817952 were at increased risk for UC in all age groups (P = 0.009).
Conclusions:
Our study provides evidence of the significant overexpression of the CXCR3 axis in active IBD, suggesting it has a role in IBD pathogenesis. The rs6817952 A variant is a risk allele for pediatric CD and UC in all age groups. Therapeutic studies will have to show whether the blockade of chemokine receptors such as CXCR3 can modulate intestinal inflammation in a clinical application.
Related Concept Videos
01:25Inflammatory Bowel Disease III: Crohn's Disease
01:30Inflammatory Bowel Disease II: Crohn's Disease
Inflammatory bowel disease, commonly known as IBD, refers to a collection of disorders that lead to persistent inflammation of the gastrointestinal tract. The two types of IBD are ulcerative colitis, which impacts the colon, and Crohn's disease, which can involve any part of the gastrointestinal segment.
Crohn's disease
Crohn's disease is a chronic, systemic inflammatory bowel disease (IBD) that predominantly affects the gastrointestinal tract. It is marked by transmural...
01:20Inflammatory Bowel Disease II: Ulcerative Colitis
01:20Inflammatory Bowel Disease IV: Clinical Manifestations
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...