Loss of Adenomatous polyposis coli function renders intestinal epithelial cells resistant to the cytokine IL-22

Yu Chen, Maud Vandereyken, Ian Newton, Ignacio Moraga Gonzalez, Inke Nathke (Lead / Corresponding author), Mahima Swamy (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)
139 Downloads (Pure)


Interleukin-22 (IL-22) is a critical immune defence cytokine that maintains intestinal homeostasis and promotes wound healing and tissue regeneration, which can support the growth of colorectal tumours. Mutations in the adenomatous polyposis coli gene (Apc) are a major driver of familial colorectal cancers (CRCs). How IL-22 contributes to APC-mediated tumorigenesis is poorly understood. To investigate IL-22 signalling in wild-type (WT) and APC-mutant cells, we performed RNA sequencing (RNAseq) of IL-22-treated murine small intestinal epithelial organoids. In WT epithelia, antimicrobial defence and cellular stress response pathways were most strongly induced by IL-22. Surprisingly, although IL-22 activates signal transducer and activator of transcription 3 (STAT3) in APC-mutant cells, STAT3 target genes were not induced. Our analyses revealed that ApcMin/Min cells are resistant to IL-22 due to reduced expression of the IL-22 receptor, and increased expression of inhibitors of STAT3, particularly histone deacetylases (HDACs). We further show that IL-22 increases DNA damage and genomic instability, which can accelerate cellular transition from heterozygosity (ApcMin/+) to homozygosity (ApcMin/Min) to drive tumour formation. Our data reveal an unexpected role for IL-22 in promoting early tumorigenesis while excluding a function for IL-22 in transformed epithelial cells.

Original languageEnglish
Article numbere3000540
Pages (from-to)1-23
Number of pages23
JournalPLoS Biology
Issue number11
Publication statusPublished - 26 Nov 2019


  • Adenomatous polyposis coli
  • Interleukin-22 receptor
  • antimicrobial defence
  • colorectal cancer
  • intestinal epithelium
  • STAT3
  • oxidative stress
  • DNA damage response

ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry,Genetics and Molecular Biology
  • General Immunology and Microbiology
  • General Neuroscience


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