Department of Science and Environment, Roskilde University, Denmark.
Department of Clinical Immunology, Naestved Hospital, Denmark.
FEBS Open Bio. 2021 Jun;11(6):1638-1644. doi: 10.1002/2211-5463.13161. Epub 2021 May 2.
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.
白细胞介素-33（IL-33）的失调与几种自身免疫和炎症性疾病的发病机制有关，但很少有研究检查 IL33 基因的转录调控。在肠道中，基因调节受转录因子网络控制，其中肠特异性转录因子 CDX2 是关键组成部分。在这项研究中，我们研究了 CDX2 是否调节 IL33 mRNA 的表达。我们检查了来自健康人类和上皮细胞系的原代结肠上皮细胞中的 IL33 mRNA 表达水平，揭示了原代结肠和 LS174T 细胞中高表达水平。结合 LS174T 细胞中的基因组学数据（ChIP-seq、RNA-seq）和 IL33 启动子分析，发现 IL33 基因中的内含子增强子活性依赖于 CDX2 的表达。Western blot 和 qRT-PCR 证实，IL33 的表达呈 CDX2 浓度依赖性上调，从而首次提供了 CDX2 调节 IL33 表达的证据。
