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

FEBS Open Bio

Ole Birger Pedersen¹  Jakob Benedict Seidelin²  Mehmet Coskun³  Eric Paul Bennett⁴  Jesper Thorvald Troelsen⁵  Katja Dahlgaard⁵  Sylvester Larsen⁶  Johanne Davidsen⁷  Claus Henrik Nielsen⁸ 

[1]Department of Clinical Immunology, Næstved Hospital, Denmark

[2]Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark

[3]Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark

[4]Department of Biology, The Bioinformatics Centre, Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Denmark

[5]Department of Odontology, Copenhagen Center for Glycomics, Faculty of Health Sciences, University of Copenhagen, Denmark

[6]Department of Science and Environment, Roskilde University, Denmark

[7]Department of Science and Environment, Roskilde University, Denmark

[8]Department of Clinical Immunology, Næstved Hospital, Denmark

[9]Department of Science and Environment, Roskilde University, Denmark

[10]Department of Surgical Gastroenterology, Zealand University Hospital, Køge, Denmark

[11]Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Section 7521, Copenhagen University Hospital Rigshospitalet, Denmark

关键词: Caudal;    gene regulation;    inflammatory bowel disease;    interleukin‐33;    intestinal regulation;    transcriptional control;   

DOI  :  10.1002/2211-5463.13161

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY