Nod2: A Critical Regulator of Ileal Microbiota and Crohn's Disease.
Nod2: A Critical Regulator of Ileal Microbiota and Crohn's Disease.
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DOI：
10.3389/fimmu.2016.00367
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发表时间：
2016
影响因子：
7.3
通讯作者：
Kobayashi KS
中科院分区：
文献类型：
--
作者：
Sidiq T;Yoshihama S;Downs I;Kobayashi KS
人体肠道内存在大量的细菌群落，包括共生菌、共生菌和致病菌，它们不断与肠道免疫系统相互作用。这种相互作用激发了免疫应答的非病理基础水平，并有助于塑造肠道免疫系统和细菌群落。近年来对人体肠道菌群的研究揭示了肠道菌群在包括克罗恩病（CD）在内的全身性和肠道疾病发病机制中的重要作用。NOD2在小肠微生物群的调节中起着关键作用。NOD2在回肠Paneth细胞中高度表达，其通过分泌抗菌化合物为回肠微生物群的调节提供关键机制。CD患者的基因组图谱显示NOD2功能缺失突变与回肠CD相关。全基因组关联研究进一步证明NOD2是与回肠CD相关的最关键的遗传因子之一。回肠中的细菌群落确实在Nod2缺陷小鼠中失调。Nod2缺陷的回肠上皮细胞表现出杀菌能力受损。因此，通过NOD2突变改变的回肠微生物群和粘膜免疫之间的相互作用在CD患者的疾病易感性和发病机制中起重要作用，从而将NOD2描述为回肠微生物群和CD的关键调节剂。
The human intestinal tract harbors large bacterial community consisting of commensal, symbiotic, and pathogenic strains, which are constantly interacting with the intestinal immune system. This interaction elicits a non-pathological basal level of immune responses and contributes to shaping both the intestinal immune system and bacterial community. Recent studies on human microbiota are revealing the critical role of intestinal bacterial community in the pathogenesis of both systemic and intestinal diseases, including Crohn’s disease (CD). NOD2 plays a key role in the regulation of microbiota in the small intestine. NOD2 is highly expressed in ileal Paneth cells that provide critical mechanism for the regulation of ileal microbiota through the secretion of anti-bacterial compounds. Genome mapping of CD patients revealed that loss of function mutations in NOD2 are associated with ileal CD. Genome-wide association studies further demonstrated that NOD2 is one of the most critical genetic factor linked to ileal CD. The bacterial community in the ileum is indeed dysregulated in Nod2-deficient mice. Nod2-deficient ileal epithelia exhibit impaired ability of killing bacteria. Thus, altered interactions between ileal microbiota and mucosal immunity through NOD2 mutations play significant roles in the disease susceptibility and pathogenesis in CD patients, thereby depicting NOD2 as a critical regulator of ileal microbiota and CD.
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影响因子：
3.7
作者：
Dalmasso G;Nguyen HT;Yan Y;Charrier-Hisamuddin L;Sitaraman SV;Merlin D
通讯作者：
Merlin D
影响因子：
8
作者：
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通讯作者：
Boirivant M
影响因子：
64.8
作者：
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影响因子：
8
作者：
Dignass, A.;Van Assche, G.;Travis, S. P. L.
通讯作者：
Travis, S. P. L.
影响因子：
30.5
作者：
Bernink, Jochem H.;Peters, Charlotte P.;Spits, Hergen
通讯作者：
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