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Distinct Retrotransposon Transcriptome in Pediatric Crohn's Disease
Qing Chen1, Colton McNinch2, Eve May1
1Clinical Microbiome Unit, Laboratory of Host Immunity and Microbiome, Division of Intramural Research National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States.
Medrxiv : the Preprint Server for Health Sciences
|June 26, 2025
Summary
Retrotransposon expression differs in children with Crohn's disease (CD), particularly in ileal biopsies. Fifteen specific retrotransposon loci were consistently downregulated in CD patients compared to controls, suggesting potential therapeutic targets.
Area of Science:
- Genomics
- Molecular Biology
- Immunology
Background:
- Crohn's disease (CD) is an autoimmune gastrointestinal disorder with complex, partially understood causes.
- Retrotransposons, mobile genetic elements, are implicated in autoimmune and inflammatory diseases.
- This study investigates retrotransposon expression in pediatric CD.
Purpose of the Study:
- To explore and quantify the expression of retrotransposons in children diagnosed with Crohn's disease.
- To identify specific retrotransposon loci that are differentially expressed in CD ileal and rectal tissues.
- To validate findings in independent pediatric cohorts.
Main Methods:
- High-throughput RNA sequencing (RNAseq) was used to analyze retrotransposon expression at the locus level.
- Ileal and rectal biopsies from treatment-naïve pediatric CD patients and non-IBD controls were analyzed.
- Expression data was validated using public datasets (GSE57945, GSE117993).
Main Results:
- Distinct retrotransposon expression patterns were observed between CD patients and controls in ileal biopsies.
- 118 differentially expressed retrotransposon loci were identified in ileal CD samples (74 LINE-1, 44 HERV).
- Fifteen retrotransposon loci, including HERV and L1PA types, were consistently downregulated in ileal CD tissues across both datasets.
Conclusions:
- The retrotransposon transcriptome in pediatric CD ileal biopsies significantly differs from non-IBD controls.
- Consistent downregulation of 15 retrotransposon loci in CD ileal tissue warrants further investigation into their regulatory roles.
- These findings may offer new perspectives for developing innovative therapeutic strategies for Crohn's disease.
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