CARD15/NOD2 is required for Peyer's patches homeostasis in mice.
CARD15/NOD2 is required for Peyer's patches homeostasis in mice.
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Peyer补丁在小鼠中需要CARD15/NOD2。
DOI：
10.1371/journal.pone.0000523
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发表时间：
2007-06-13
期刊：
影响因子：
3.7
通讯作者：
Hugot, Jean-Pierre
中科院分区：
文献类型：
--
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
CARD15/NOD2突变与克罗恩病（CD）和移植物抗宿主病（GVHD）的易感性相关。CD和GVHD被怀疑与Peyer’s patches （PP）和孤立淋巴滤泡（LFs）功能障碍有关。因此，我们使用一种新的小鼠模型来分析Card15/Nod2 （KO）基因在这些淋巴组织形成以及实验性结肠炎发展中的影响。在第4、12和52周，KO小鼠的PPs和LFs数量较高，而在出生时没有观察到差异。在第4周和第12周，用流式细胞术和免疫组织化学分析PPs的大小和细胞组成。KO小鼠的PPs增大，M细胞和CD4+ t细胞比例增加。通过ELISA检测，KO小鼠的TNFα、IFNγ、il - 12和il - 4的浓度也较高。与此相反，KO小鼠的回肠和脾脏无pp差异不大。通过室内实验，我们发现这种PP表型与细胞旁通透性和酵母/细菌易位的增加有关。最后，KO小鼠更容易发生TNBS诱导的结肠炎。Card15/Nod2缺乏可诱导PPs发育和功能异常，其特征是免疫反应过度和通透性增加。这些观察结果提供了分子缺陷与人类CARD15/NOD2相关疾病：CD和GVHD之间的全面联系。
CARD15/NOD2 mutations are associated with susceptibility to Crohn's Disease (CD) and Graft Versus Host Disease (GVHD). CD and GVHD are suspected to be related with the dysfunction of Peyer's patches (PP) and isolated lymphoid follicles (LFs). Using a new mouse model invalidated for Card15/Nod2 (KO), we thus analysed the impact of the gene in these lymphoid formations together with the development of experimental colitis. At weeks 4, 12 and 52, the numbers of PPs and LFs were higher in KO mice while no difference was observed at birth. At weeks 4 and 12, the size and cellular composition of PPs were analysed by flow cytometry and immunohistochemistry. PPs of KO mice were larger with an increased proportion of M cells and CD4+ T-cells. KO mice were also characterised by higher concentrations of TNFα, IFNγ, IL12 and IL4 measured by ELISA. In contrast, little differences were found in the PP-free ileum and the spleen of KO mice. By Ussing chamber experiments, we found that this PP phenotype is associated with an increased of both paracellular permeability and yeast/bacterial translocation. Finally, KO mice were more susceptible to the colitis induced by TNBS. Card15/Nod2 deficiency induces an abnormal development and function of the PPs characterised by an exaggerated immune response and an increased permeability. These observations provide a comprehensive link between the molecular defect and the Human CARD15/NOD2 associated disorders: CD and GVHD.
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影响因子：
24.5
作者：
Fujimura, Y;Kamoi, R;Iida, M
通讯作者：
Iida, M
影响因子：
2.2
作者：
Hess, DJ;Henry-Stanley, MJ;Wells, CL
通讯作者：
Wells, CL
影响因子：
29.4
作者：
KATZ, KD;HOLLANDER, D;ROTTER, JI
通讯作者：
ROTTER, JI
DOI：
10.1084/jem.189.8.1169
发表时间：
1999-04-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Dohi T;Fujihashi K;Rennert PD;Iwatani K;Kiyono H;McGhee JR
通讯作者：
McGhee JR
影响因子：
9.8
作者：
Lesage, S;Zouali, H;Hugot, JP
通讯作者：
Hugot, JP