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MicroRNA-150 controls differentiation of intraepithelial lymphocytes through TGF-β receptor II regulation
Journal of Allergy and Clinical Immunology ( IF 14.2 ) Pub Date : 2017-08-07 , DOI: 10.1016/j.jaci.2017.07.019
Sang-Hwan Seo , Min Seong Jang , Doo-Jin Kim , Seok-Min Kim , Se-Chan Oh , Cho-Rok Jung , Yunji Park , Sang-Jun Ha , Haiyoung Jung , Young-Jun Park , Suk Ran Yoon , Inpyo Choi , Tae-Don Kim

Background

Intraepithelial lymphocytes (IELs) in the intestines play pivotal roles in maintaining the integrity of the mucosa, regulating immune cells, and protecting against pathogenic invasion. Although several extrinsic factors, such as TGF-β, have been identified to contribute to IEL generation, intrinsic regulatory factors have not been determined fully.

Objective

Here we investigated the regulation of IEL differentiation and the underlying mechanisms in mice.

Methods

We analyzed IELs and the expression of molecules associated with IEL differentiation in wild-type control and microRNA (miRNA)-150 knockout mice. Methotrexate was administered to mice lacking miR-150 and control mice.

Results

miR-150 deficiency reduced the IEL population in the small intestine and increased susceptibility to methotrexate-induced mucositis. Evaluation of expression of IEL differentiation–associated molecules showed that miR-150–deficient IELs exhibited decreased expression of TGF-β receptor (TGF-βR) II, CD103, CD8αα, and Runt-related transcription factor 3 in all the IEL subpopulations. The reduced expression of TGF-βRII in miR-150–deficient IELs was caused by increased expression of c-Myb/miR-20a. Restoration of miR-150 or inhibition of miR-20a recovered the TGF-βRII expression.

Conclusion

miR-150 is an intrinsic regulator of IEL differentiation through TGF-βRII regulation. miR-150–mediated IEL generation is crucial for maintaining intestinal integrity against anticancer drug–induced mucositis.



中文翻译:

MicroRNA-150通过TGF-β受体II调控调控上皮内淋巴细胞的分化

背景

肠道中的上皮内淋巴细胞(IEL)在维持粘膜完整性,调节免疫细胞和防止病原体侵袭中起关键作用。尽管已确定几种外在因素(例如TGF-β)有助于IEL的产生,但尚未完全确定内在的调节因素。

客观的

在这里,我们研究了小鼠IEL分化的调控及其潜在机制。

方法

我们分析了IELs和野生型对照和microRNA(miRNA)-150基因敲除小鼠中与IEL分化相关的分子的表达。将甲氨蝶呤施用于缺乏miR-150的小鼠和对照小鼠。

结果

miR-150缺乏症减少了小肠的IEL种群,并增加了对甲氨蝶呤诱发的粘膜炎的敏感性。对IEL分化相关分子表达的评估表明,miR-150缺失的IEL在所有IEL亚群中均表现出TGF-β受体(TGF-βR)II,CD103,CD8αα和Runt相关转录因子3的表达降低。缺乏miR-150的IEL中TGF-βRII的表达减少是由于c-Myb / miR-20a的表达增加所致。恢复miR-150或抑制miR-20a恢复了TGF-βRII表达。

结论

miR-150是通过TGF-βRII调控IEL分化的内在调控因子。miR-150介导的IEL生成对于维持抗癌药诱发的粘膜炎的肠道完整性至关重要。

更新日期:2017-08-07
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