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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer 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.

OriginalsprogEngelsk
TidsskriftFEBS Open Bio
Vol/bind11
Udgave nummer6
Sider (fra-til)1638-1644
Antal sider7
DOI
StatusUdgivet - jun. 2021

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