Gut commensals suppress interleukin-2 production through microRNA-200/BCL11B and microRNA-200/ETS-1 axes in lamina propria leukocytes of murine large intestine
Gut commensals suppress interleukin-2 production through microRNA-200/BCL11B and microRNA-200/ETS-1 axes in lamina propria leukocytes of murine large intestine
复制标题
肠道共生体通过小鼠大肠固有层白细胞中的 microRNA-200/BCL11B 和 microRNA-200/ETS-1 轴抑制白细胞介素 2 的产生
DOI：
10.1016/j.bbrc.2020.10.103
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发表时间：
2021
影响因子：
3.1
通讯作者：
Sonoyama Kei
中科院分区：
文献类型：
--
作者：
Ohsaka Fumina;Karatsu Yugo;Kadota Yoshihiro;Tochio Takumi;Takemura Naoki;Sonoyama Kei
microRNA（miRNAs）在微生物群如何影响宿主肠道免疫系统中的作用尚未完全了解。我们比较了无菌（GF）和无特定病原体（SPF）小鼠大肠固有层白细胞（LPL）中miRNA和mRNA的表达谱。微阵列分析显示GF和SPF小鼠的miRNAs和mRNAs表达谱不同。定量真实的时间PCR（qRT-PCR）结果显示，SPF小鼠miR-200家族成员的表达水平显著高于GF小鼠;计算机预测结果显示，miR-200家族下调了Bcl 11 b、Ets 1、Gbp 7、Stat 5 b和Zeb 1基因的表达。Western blotting结果显示，SPF小鼠大肠LPL中BCL 11 B和ETS-1的表达显著低于GF小鼠，而ZEB 1的表达则无显著差异。用佛波醇12-肉豆蔻酸酯13-乙酸酯和离子霉素刺激培养的LPL 24 h后，SPF小鼠中白细胞介素（IL）-2的产生显著低于GF小鼠。GF小鼠的常规化在大肠LPL中miR-200家族成员及其靶基因的表达和IL-2产生方面基本上概括了SPF小鼠。考虑到BCL 11B和ETS-1作为转录因子激活IL-2基因的报道，我们认为肠黏膜的存在抑制了大肠LPL中IL-2的产生，至少部分是通过miR-200家族成员下调Bcl-11和ETS-1基因的转录后表达。
The role of microRNAs (miRNAs) in how microbiota influence the host intestinal immune system is not fully understood. We compared the expression profiles of miRNAs and mRNAs in lamina propria leukocytes (LPL) in the large intestines of germ-free (GF) and specific pathogen-free (SPF) mice. Microarray analysis revealed different expression profiles of miRNAs and mRNAs between GF and SPF mice. Quantitative real time-PCR (qRT-PCR) showed that the level of miR-200 family members was significantly higher in SPF mice than in GF mice.In silicoprediction followed by qRT-PCR suggested thatBcl11b, Ets1,Gbp7,Stat5b,andZeb1genes were downregulated by the miR-200 family. Western blotting revealed that the expression of BCL11B and ETS-1, but not ZEB1, in large intestinal LPL was significantly lower in SPF mice than in GF mice. Interleukin (IL)-2 production in cultured LPL upon stimulation with phorbol 12-myristate 13-acetate and ionomycin for 24 h was significantly lower in SPF mice than in GF mice. Conventionalization of GF mice substantially recapitulated SPF mice in terms of the expression of miR-200 family members and their target genes and IL-2 production in large intestinal LPL. Considering that BCL11B and ETS-1 reportedly function as transcription factors to activate theIl2gene, we propose that the presence of gut commensals suppresses IL-2 production in large intestinal LPL, at least in part through post-transcriptional downregulation ofBcl11bandEts1genes by miR-200 family members.