Distinct Retrotransposon Transcriptome in Pediatric Crohn's Disease

Area of Science:

• Genomics
• Molecular Biology
• Immunology

Background:

• Crohn's disease (CD) is a complex autoimmune disorder affecting the gastrointestinal tract.
• The precise mechanisms underlying CD pathogenesis remain incompletely understood.
• Retrotransposons, mobile genetic elements, are implicated in inflammatory and autoimmune diseases.

Purpose of the Study:

• To investigate the expression patterns of retrotransposons in pediatric patients diagnosed with Crohn's disease.
• To compare retrotransposon expression between treatment-naïve children with CD and non-inflammatory bowel disease (IBD) controls.

Main Methods:

• High-throughput RNA sequencing (RNAseq) was employed for locus-level expression analysis of LINE, SINE, and LTR-retrotransposons (human endogenous retroviruses - HERVs).
• Analysis was conducted on ileal and rectal biopsies from pediatric CD patients and age-matched controls.
• Findings were validated using public datasets (GSE57945 and GSE117993).

Main Results:

• Distinct retrotransposon expression profiles were observed between CD patients and controls in ileal biopsies, with less pronounced differences in rectal biopsies.
• A total of 118 differentially expressed retrotransposon loci were identified in the ileum (27 upregulated, 91 downregulated), including LINE-1 and HERV elements.
• Fifteen retrotransposon loci, such as HERV9N-int and L1PA4, were consistently downregulated in the ileum of CD patients across both analyzed datasets.

Conclusions:

• The retrotransposon transcriptome in pediatric CD patients shows significant alterations, particularly in the ileum.
• Consistent downregulation of 15 specific retrotransposon loci in pediatric CD ileal biopsies warrants further investigation into their regulatory roles.
• These findings may offer novel insights for developing targeted therapeutic strategies for Crohn's disease.