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Foxp3 调节性 T 细胞耗竭伴随着肠道微生物组中厚壁菌门相对丰度的增加。

Depletion of Foxp3 regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome.

机构信息

Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

出版信息

Immunology. 2020 Mar;159(3):344-353. doi: 10.1111/imm.13158. Epub 2019 Dec 12.

Abstract

A reciprocal interaction exists between the gut microbiota and the immune system. Regulatory T (Treg) cells are important for controlling immune responses and for maintaining the intestinal homeostasis but their precise influence on the gut microbiota is unclear. We studied the effects of Treg cell depletion on inflammation of the intestinal mucosa and analysed the gut microbiota before and after depletion of Treg cells using the DEpletion of REGulatory T cells (DEREG) mouse model. DNA was extracted from stool samples of DEREG mice and wild-type littermates at different time-points before and after diphtheria toxin application to deplete Treg cells in DEREG mice. The V3/V4 region of the 16S rRNA gene was used for studying the gut microbiota with Illumina MiSeq paired ends sequencing. Multidimensional scaling separated the majority of gut microbiota samples from late time-points after Treg cell depletion in DEREG mice from samples of early time-points before Treg cell depletion in these mice and from gut microbiota samples of wild-type mice. Treg cell depletion in DEREG mice was accompanied by an increase in the relative abundance of the phylum Firmicutes and by intestinal inflammation in DEREG mice 20 days after Treg cell depletion, indicating that Treg cells influence the gut microbiota composition. In addition, the variables cage, breeding and experiment number were associated with differences in the gut microbiota composition and these variables should be respected in murine studies.

摘要

肠道微生物群与免疫系统之间存在着相互作用。调节性 T(Treg)细胞对于控制免疫反应和维持肠道内稳态非常重要,但它们对肠道微生物群的确切影响尚不清楚。我们研究了 Treg 细胞耗竭对肠道黏膜炎症的影响,并使用 DEpletion of REGulatory T cells(DEREG)小鼠模型在 Treg 细胞耗竭前后分析了肠道微生物群。从 DEREG 小鼠和野生型同窝仔鼠在使用白喉毒素耗竭 Treg 细胞前后的不同时间点的粪便样本中提取 DNA。使用 Illumina MiSeq 配对末端测序研究 16S rRNA 基因的 V3/V4 区以研究肠道微生物群。多维尺度分析将 DEREG 小鼠 Treg 细胞耗竭后晚期的大多数肠道微生物群样本与这些小鼠 Treg 细胞耗竭前早期的样本以及野生型小鼠的肠道微生物群样本区分开来。DEREG 小鼠 Treg 细胞耗竭伴随着厚壁菌门相对丰度的增加和 DEREG 小鼠 Treg 细胞耗竭 20 天后的肠道炎症,表明 Treg 细胞影响肠道微生物群组成。此外,笼位、饲养和实验数量与肠道微生物群组成的差异有关,在鼠类研究中应尊重这些变量。

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