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

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.

Hepatic pannexin‐1 mediates ST2+ regulatory T cells promoting resolution of inflammation in lipopolysaccharide‐induced endotoxemia

“…62 Whether P2X7 can regulate any transcription factor that induces IL-33 expression, such as CDX2, remains unclear. 69 The exact mechanism by which P2X7 regulates IL-33 production remains unclear and represents a topic for future studies. In addition, rIL-33 pretreatment significantly protected Panx1 −/-→ WT mice against LPS-induced endotoxemia.…”

“…Another study also reported that the P2X7 receptor was involved in IL‐33 production by increasing the concentration of Ca 2+ 62 . Whether P2X7 can regulate any transcription factor that induces IL‐33 expression, such as CDX2, remains unclear 69 . The exact mechanism by which P2X7 regulates IL‐33 production remains unclear and represents a topic for future studies.…”

Tumor suppressor p53 deficiency increases tumor immunogenicity through promoting IL33-mediated anti-tumor immune responses

“…NFE2L3 can bind the regulatory sequences of the Il-33 locus and promote its expression ( 17 ) in colorectal cancer cells. CDX2 directly binds and promote the intronic enhancer activity in the IL33 gene in primary colonic epithelial cells from healthy humans and epithelial cell lines ( 18 ). Friend leukemia virus integration 1 (Fli1), whose deficiency is a predisposing factor of systemic sclerosis (SSc), occupies the IL33 promoter in dermal fibroblasts and represses IL33 expression.…”