Cytokine responsive networks in human colonic epithelial organoids unveil a molecular classification of inflammatory bowel disease

Polychronis Pavlidis, Anastasia Tsakmaki, Agatha Treveil, Katherine Li, Domenico Cozzetto, Feifei Yang, Umar Niazi, Bu Hussain Hayee, Mansoor Saqi, Joshua Friedman, Tamas Korcsmaros, Gavin Bewick, Nick Powell

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

Interactions between the epithelium and the immune system are critical in the pathogenesis of inflammatory bowel disease (IBD). In this study, we mapped the transcriptional landscape of human colonic epithelial organoids in response to different cytokines responsible for mediating canonical mucosal immune responses. By profiling the transcriptome of human colonic organoids treated with the canonical cytokines interferon gamma, interleukin-13, -17A, and tumor necrosis factor alpha with next-generation sequencing, we unveil shared and distinct regulation patterns of epithelial function by different cytokines. An integrative analysis of cytokine responses in diseased tissue from patients with IBD (n = 1,009) reveals a molecular classification of mucosal inflammation defined by gradients of cytokine-responsive transcriptional signatures. Our systems biology approach detected signaling bottlenecks in cytokine-responsive networks and highlighted their translational potential as theragnostic targets in intestinal inflammation.

Original languageEnglish
Article number111439
Pages (from-to)111439
JournalCell Reports
Volume40
Issue number13
DOIs
Publication statusPublished - 27 Sept 2022

Keywords

  • Colon/pathology
  • Cytokines
  • Humans
  • Inflammation/pathology
  • Inflammatory Bowel Diseases/pathology
  • Interferon-gamma/pharmacology
  • Interleukin-13
  • Intestinal Mucosa/pathology
  • Organoids/pathology
  • Tumor Necrosis Factor-alpha

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