Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells.
Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells.
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DOI：
10.1038/s41598-018-32583-z
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发表时间：
2018-09-24
影响因子：
4.6
通讯作者：
De Filippo C
中科院分区：
文献类型：
--
作者：
Butera A;Di Paola M;Pavarini L;Strati F;Pindo M;Sanchez M;Cavalieri D;Boirivant M;De Filippo C
核苷酸结合寡聚化结构域2（NOD 2）突变与克罗恩病风险增加相关。在以前的研究中，我们已经表明，与Nod 2 +/+小鼠相比，Nod 2 −/−小鼠表现出固有层（LP）CD 4 + T细胞+Foxp 3 −调节细胞的比例增加，而CD 4 + Foxp 3+调节细胞不受影响。在这里，我们通过16 S rRNA焦磷酸测序研究了Nod 2肠道微生物群，在稳态和TNBS-结肠炎诱导后，在单独饲养或共同饲养的小鼠中，将微生物谱与LP调节性T细胞比例和组织细胞因子含量相关联。我们发现，在8周龄的Nod 2 −/−小鼠中，Rikenella和Alistipes（Rikenellaceae）的富集与CD 4 + CD 4 + Foxp 3 −细胞比例的增加和TNBS结肠炎的严重程度降低有关。在共同饲养的小鼠中，Nod 2 +/+小鼠获得立克次氏体与CD 4 + T细胞+Foxp 3 −比例增加和结肠炎严重程度降低相关。严重的结肠炎与革兰氏阴性致病菌（埃希氏菌和肠球菌）的富集有关，而不太严重的结肠炎与保护性细菌（Barnesiella，Odoribacter和Clostridium IV）有关。环境因素作用于遗传背景，根据其对微生物群的影响而产生不同的结果，以不同的方式易患炎症。这些结果为在具有NOD 2多态性的炎症性肠病患者中重建生态平衡的治疗尝试开辟了新的场景。
Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn’s Disease. In previous studies, we have shown that Nod2−/− mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3− regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2−/− mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3− cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3− proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms.
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影响因子：
8
作者：
Amendola A;Butera A;Sanchez M;Strober W;Boirivant M
通讯作者：
Boirivant M
DOI：
10.1126/science.1198469
发表时间：
2011-01-21
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Atarashi K;Tanoue T;Shima T;Imaoka A;Kuwahara T;Momose Y;Cheng G;Yamasaki S;Saito T;Ohba Y;Taniguchi T;Takeda K;Hori S;Ivanov II;Umesaki Y;Itoh K;Honda K
通讯作者：
Honda K
DOI：
10.1099/ijs.0.015016-0
发表时间：
2010-07
影响因子：
2.8
作者：
Clavel T;Duck W;Charrier C;Wenning M;Elson C;Haller D
通讯作者：
Haller D
影响因子：
7.3
作者：
Basson A;Trotter A;Rodriguez-Palacios A;Cominelli F
通讯作者：
Cominelli F
Peyer补丁在小鼠中需要CARD15/NOD2。
影响因子：
3.7
作者：
Barreau, Frederick;Meinzer, Ulrich;Chareyre, Fabrice;Berrebi, Dominique;Niwa-Kawakita, Michiko;Dussaillant, Monique;Foligne, Benoit;Ollendorff, Vincent;Heyman, Martine;Bonacorsi, Stephane;Lesuffleur, Thecla;Sterkers, Ghislaine;Giovannini, Marco;Hugot, Jean-Pierre
通讯作者：
Hugot, Jean-Pierre