Interleukin 33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization.
Interleukin 33 regulates gene expression in intestinal epithelial cells independently of its nuclear localization.
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DOI：
10.1016/j.cyto.2018.08.009
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发表时间：
2018-11
期刊：
影响因子：
3.8
通讯作者：
Lira SA
中科院分区：
文献类型：
--
作者：
He Z;Chen L;Furtado GC;Lira SA
白细胞介素33 （il - 33）是一种细胞因子，存在于细胞外间隙（成熟il - 33）或细胞核（全长il - 33）。据报道，在肠道炎症和癌症期间，肠上皮细胞（IEC）中存在IL33的核积累，但这种核形式的功能作用尚不清楚。为了研究核il - 33在IEC中的作用，我们培育了在肠上皮中表达全长il - 33的转基因小鼠（Vfl33小鼠）。上皮中全长IL33的表达导致IL33蛋白在细胞核内的积累和分泌。IEC过表达全长IL33不会促进肠道炎症，但会诱导IEC和固有层淋巴细胞（LPL）中与炎症性肠病（IBD）基因表达负相关的基因表达。由于IL33受体ST2是通过IEC表达的，因此成熟和全长形式都有可能介导这种作用。为了明确研究核il - 33的转录作用，我们将Vfl33小鼠与ST2-缺陷小鼠杂交。ST2缺失完全消除了IL33表达引起的转录效应，这表明IL33对IEC的转录效应是由其成熟而非核形式介导的。
Interleukin 33 (IL33) is a cytokine found in the extracellular space (mature IL33) or in the cell nucleus (full-length IL33). Nuclear accumulation of IL33 has been reported in intestinal epithelial cells (IEC) during intestinal inflammation and cancer, but a functional role for this nuclear form remains unclear. To study the role of nuclear IL33 in IEC, we generated transgenic mice expressing full-length IL33 in the intestinal epithelium (Vfl33 mice). Expression of full-length IL33 in the epithelium resulted in accumulation of IL33 protein in the nucleus and secretion of IL33. Over-expression of full-length IL33 by IEC did not promote gut inflammation, but induced expression of genes in the IEC and lamina propria lymphocytes (LPL) that correlated negatively with genes expressed in inflammatory bowel diseases (IBD). Because the IL33 receptor ST2 is expressed by IEC, there was the potential that both the mature and full-length forms could mediate this effect. To specifically interrogate the transcriptional role of nuclear IL33, we intercrossed the Vfl33 mice with ST2- deficient mice. ST2 deficiency completely abrogated the transcriptional effects elicited by IL33 expression, suggesting that the transcriptional effects of IL33 on IEC are mediated by its mature, not its nuclear form.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
8.7
作者：
Dinarello CA
通讯作者：
Dinarello CA
DOI：
10.1016/j.bbrc.2009.12.107
发表时间：
2010-01-15
影响因子：
3.1
作者：
Ali, Shafaqat;Nguyen, Dang Quan;Martin, Michael Uwe
通讯作者：
Martin, Michael Uwe
影响因子：
6
作者：
Baekkevold, ES;Roussigné, M;Girard, JP
通讯作者：
Girard, JP