CDX2 regulates interleukin-33 gene expression in intestinal epithelial cells (LS174T)

Sylvester Larsen, Jakob Benedict Seidelin, Johanne Davidsen, Katja Dahlgaard, Claus Henrik Nielsen, Eric Paul Bennett, Ole Birger Pedersen, Mehmet Coskun, Jesper Thorvald Troelsen*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Dysregulation of interleukin-33 (IL-33) has been implicated in the pathogenesis of several autoimmune and inflammatory diseases, but few studies have examined transcriptional regulation of the IL33 gene. In the intestines, gene regulation is controlled by a transcription factor network of which the intestinal-specific transcription factor CDX2 is a key component. In this study, we investigated whether CDX2 regulates IL33 mRNA expression. We examined IL33 mRNA expression in primary colonic epithelial cells from healthy humans and epithelial cell lines, revealing high expression levels in primary colonic and LS174T cells. Combining genomics data (ChIP-seq, RNA-seq) and IL33 promoter analyses in LS174T cells revealed intronic enhancer activity in the IL33 gene that is dependent on CDX2 expression. Western blotting and qRT-PCR confirmed that IL33 expression is upregulated in a CDX2 concentration-dependent manner, thereby providing the first evidence that CDX2 regulates the expression of IL33.

Original languageEnglish
JournalFEBS Open Bio
Volume11
Issue number6
Pages (from-to)1638-1644
Number of pages7
DOIs
Publication statusPublished - Jun 2021

Keywords

  • Caudal-related homeobox transcription factor 2
  • gene regulation
  • inflammatory bowel disease
  • interleukin-33
  • intestinal regulation
  • transcriptional control

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