当前位置: X-MOL 学术Immunol. Cell Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Early-life exposure to gut microbiota from disease-protected mice does not impact disease outcome in type 1 diabetes susceptible NOD mice.
Immunology and Cell Biology ( IF 4 ) Pub Date : 2018-09-08 , DOI: 10.1111/imcb.12201
Jane A Mullaney 1 , Juliette E Stephens 1 , Brooke E Geeling 1 , Emma E Hamilton-Williams 1
Affiliation  

The microbial community making up the gut microbiota can profoundly influence intestinal homeostasis and immune system development, and is believed to influence the development of complex diseases including type 1 diabetes (T1D). T1D susceptible nonobese diabetic (NOD) mice have been shown to harbor a distinct microbiota to disease-protected mice. We hypothesized that the T1D susceptible genetic background of NOD mice would be resistant to the introduction of a C57BL/6-derived microbiota. NOD and C57BL/6 mice were cohoused either continually from birth, from birth until weaning or from weaning onwards, allowing transfer of microbiota between the mice. Cohousing NOD with C57BL/6 mice from before birth, resulted in moderate changes to the gut microbiota, whereas initiating cohousing at weaning only led to minimal changes. Terminating cohousing at weaning reduced the changes in the microbiota composition. However, diabetes onset was not significantly delayed and there was no reduction in intestinal inflammation or the proportion of regulatory T cells in the cohoused NOD mice. However, insulin but not islet-specific glucose-6-phosphatase catalytic subunit-related protein-specific CD8+ T cells were reduced by cohousing suggesting an epitope-specific modulation of the autoreactive response by the gut microbiota. These results suggest that the T1D susceptible genetic background of the NOD mouse was resistant to the introduction of a C57BL/6-derived microbiota.

中文翻译:

受疾病保护的小鼠在生命早期暴露于肠道菌群不会影响1型糖尿病易感性NOD小鼠的疾病结局。

组成肠道菌群的微生物群落可以深刻影响肠道的动态平衡和免疫系统的发育,并被认为会影响包括1型糖尿病(T1D)在内的复杂疾病的发展。T1D易感非肥胖糖尿病(NOD)小鼠已显示出对疾病保护小鼠具有独特的微生物群。我们假设NOD小鼠的T1D易感遗传背景将对源自C57BL / 6的微生物群的引入具有抗性。从出生开始,从出生到断奶或从断奶开始连续饲养NOD和C57BL / 6小鼠,以使微生物群在小鼠之间转移。从出生前开始与C57BL / 6小鼠换食NOD,会导致肠道菌群发生适度变化,而在断奶时开始换食则只会导致最小的变化。在断奶时终止鸡舍减少了微生物群组成的变化。然而,糖尿病的发作并没有明显延迟,在共同饲养的NOD小鼠中肠道炎症或调节性T细胞的比例没有减少。但是,胰岛素的代谢减少了胰岛素,但胰岛特异性的葡萄糖-6磷酸酶催化的亚基相关的蛋白质特异性的CD8 + T细胞却没有减少,这表明肠道菌群对自身反应的抗原决定簇特异性调节。这些结果表明,NOD小鼠的T1D易感遗传背景对引入C57BL / 6衍生的微生物群具有抵抗力。并没有明显延迟糖尿病的发作,并且在共同饲养的NOD小鼠中肠道炎症或调节性T细胞的比例没有减少。但是,胰岛素的代谢减少了胰岛素,但胰岛特异性的葡萄糖-6磷酸酶催化的亚基相关的蛋白质特异性的CD8 + T细胞却没有减少,这表明肠道菌群对自身反应的抗原决定簇特异性调节。这些结果表明,NOD小鼠的T1D易感遗传背景对引入C57BL / 6衍生的微生物群具有抵抗力。并没有明显延迟糖尿病的发作,并且在共同饲养的NOD小鼠中肠道炎症或调节性T细胞的比例没有减少。但是,胰岛素的代谢减少了胰岛素,但胰岛特异性的葡萄糖-6磷酸酶催化的亚基相关的蛋白质特异性的CD8 + T细胞却没有减少,这表明肠道菌群对自身反应的抗原决定簇特异性调节。这些结果表明,NOD小鼠的T1D易感遗传背景对引入C57BL / 6衍生的微生物群具有抵抗力。
更新日期:2019-11-01
down
wechat
bug