Gluten-free diet exposure prohibits pathobiont expansion and gluten sensitive enteropathy in B cell deficient JH-/- mice.
Gluten-free diet exposure prohibits pathobiont expansion and gluten sensitive enteropathy in B cell deficient JH-/- mice.
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DOI：
10.1371/journal.pone.0264977
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发表时间：
2022
期刊：
影响因子：
3.7
通讯作者：
Kubinak JL
中科院分区：
文献类型：
--
作者：
Mohammed AD;Hall N;Chatzistamou I;Jolly A;Kubinak JL
在人类中，乳糜泻（CeD）是一种局限于小肠（十二指肠）的T细胞驱动的谷蛋白敏感性肠病（GSE）。谷蛋白和自身抗原特异性抗体的存在是CeD的常用诊断生物标志物，并被认为在GSE发病机制中发挥作用。以前，我们已经描述了一个明显的T细胞介导的GSE在CD 19-/-小鼠，这发展弱和异常的B细胞反应。在这里，我们扩展了这一观察，并使用完全B细胞缺乏的小鼠模型（JH-/-小鼠），以表明缺乏体液免疫反应也促进GSE的发展。此外，小肠中微生物群落的16 S分析表明，无麸质饮食抑制小肠中厌氧菌的扩张和特定致病菌在小肠中的定植。最后，我们还观察到喂食富含麸质饮食的小鼠的SI肠病与几种微生物肽酶基因的丰度呈正相关，这支持麸质的细菌代谢可能是我们模型中GSE的重要驱动因素。总的来说，我们的实验结果表明，JH-/-小鼠将是一个有用的资源，研究人员寻求经验性地描述体液免疫对GSE发病机制的贡献，并支持体液免疫促进对麸质耐受性的假设。
In humans, celiac disease (CeD) is a T-cell-driven gluten-sensitive enteropathy (GSE) localized to the small bowel (duodenum). The presence of antibodies specific for gluten- and self-antigens are commonly used diagnostic biomarkers of CeD and are considered to play a role in GSE pathogenesis. Previously, we have described an apparent T-cell-mediated GSE in CD19-/- mice, which develop weak and abnormal B cell responses. Here, we expand on this observation and use a mouse model of complete B cell deficiency (JH-/- mice), to show that absence of a humoral immune response also promotes development of a GSE. Furthermore, 16S analysis of microbial communities in the small intestine demonstrates that a gluten-free diet suppresses the expansion of anaerobic bacteria in the small intestine and colonization of the small intestine by a specific pathobiont. Finally, we also observe that SI enteropathy in mice fed a gluten-rich diet is positively correlated with the abundance of several microbial peptidase genes, which supports that bacterial metabolism of gluten may be an important driver of GSE in our model. Collectively, results from our experiments indicate that JH-/- mice will be a useful resource to investigators seeking to empirically delineate the contribution of humoral immunity on GSE pathogenesis, and support the hypothesis that humoral immunity promotes tolerance to gluten.
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影响因子：
3.7
作者：
Helmerhorst EJ;Zamakhchari M;Schuppan D;Oppenheim FG
通讯作者：
Oppenheim FG
影响因子：
17.1
作者：
Fadlallah, Jehane;El Kafsi, Hela;Gorochov, Guy
通讯作者：
Gorochov, Guy
影响因子：
24.5
作者：
Freitag TL;Rietdijk S;Junker Y;Popov Y;Bhan AK;Kelly CP;Terhorst C;Schuppan D
通讯作者：
Schuppan D
影响因子：
5.9
作者：
CUNNINGHAMRUNDLES, C;CARR, RI;GOOD, RA
通讯作者：
GOOD, RA
影响因子：
3.2
作者：
Berger, Martina;Sarantopoulos, Christos;Cesario, Thomas
通讯作者：
Cesario, Thomas