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

Depletion of Foxp3+ regulatory T cells is accompanied by an increase in the relative abundance of Firmicutes in the murine gut microbiome
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DOI:
10.1111/imm.13158
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发表时间:
2019-12-12
期刊:
影响因子:
6.4
通讯作者:
Buer, Jan
Buer, Jan
中科院分区:
医学2区
文献类型:
--
作者:
Kehrmann, Jan;Effenberg, Laura;Buer, Jan

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肠道微生物群和免疫系统之间存在相互作用。调节性T(Treg)细胞对于控制免疫反应和维持肠道稳态很重要,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细胞耗竭对肠粘膜炎症的影响,并使用调节性T细胞耗竭(DEREG)小鼠模型分析了Treg细胞耗竭前后的肠道微生物群。在白喉毒素应用之前和之后的不同时间点,从DEREG小鼠和野生型同窝仔的粪便样品中提取DNA,以耗尽DEREG小鼠中的Treg细胞。16 S rRNA基因的V3/V4区域用于使用Illumina MiSeq配对末端测序研究肠道微生物群。多维标度将DEREG小鼠中Treg细胞耗竭后的晚期时间点的大多数肠道微生物群样品与这些小鼠中Treg细胞耗竭前的早期时间点的样品以及野生型小鼠的肠道微生物群样品分开。DEREG小鼠中的Treg细胞耗竭伴随着厚壁菌门的相对丰度的增加以及Treg细胞耗竭后20天DEREG小鼠中的肠道炎症,表明Treg细胞影响肠道微生物群组成。此外,变量笼、育种和实验次数与肠道微生物群组成的差异相关,在小鼠研究中应考虑这些变量。
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.