Patterns of mucosal inflammation in pediatric inflammatory bowel disease: striking overexpression of IL-17A in children with ulcerative colitis

Pediatr Res. 2020 Apr;87(5):839-846. doi: 10.1038/s41390-019-0486-5. Epub 2019 Jul 1.

Abstract

Background: Aberrant immune responses play a key role in the pathogenesis of inflammatory bowel disease (IBD). Most studies conducted to delineate the underlying molecular mechanisms focus on adults; an understanding of these mechanisms in children remains to be determined. Here, cytokines and transcription factors produced by immune cells within the intestinal mucosa of pediatric patients stricken with ulcerative colitis (UC) and Crohn's disease (CD) are characterized; potential diagnostic and therapeutic targets are identified.

Methods: Fifty-two pediatric IBD and non-IBD patients were enrolled in the study. Specimens were taken during ileocolonoscopy. Expression of 16 genes that encode cytokines or transcription molecules was determined by quantitative polymerase chain reaction. Clinical data were collected via retrospective chart review.

Results: Overexpression of interleukin-17A (IL-17A) was evident in children with UC compared to both non-IBD and CD patients. IL-22 was strongly increased in UC patients only. Typical proinflammatory and immunoregulatory cytokines were pronounced in IBD patients, although to a lower extent in the latter case. Clustered gene expression enabled differentiation between UC and non-IBD patients.

Conclusion: Our findings highlight the crucial involvement of IL-17A immunity in the early course of IBD, particularly UC, and the potential value of gene panels in diagnosing pediatric IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Biopsy
  • Child
  • Child, Preschool
  • Cluster Analysis
  • Colitis, Ulcerative / metabolism*
  • Colitis, Ulcerative / physiopathology
  • Crohn Disease / metabolism*
  • Cytokines / metabolism
  • Female
  • Gene Expression Profiling
  • Humans
  • Inflammation
  • Interleukin-17 / metabolism*
  • Intestinal Mucosa / physiopathology*
  • Male
  • Retrospective Studies
  • Transcription Factors / metabolism

Substances

  • Cytokines
  • IL17A protein, human
  • Interleukin-17
  • Transcription Factors