Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis.
Toll-like receptors-mediated pathways activate inflammatory responses in the esophageal mucosa of adult eosinophilic esophagitis.
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DOI：
10.1038/s41424-018-0017-4
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发表时间：
2018-04-25
影响因子：
3.6
通讯作者：
Lucendo AJ
中科院分区：
文献类型：
--
作者：
Arias Á;Vicario M;Bernardo D;Olalla JM;Fortea M;Montalban-Arques A;Martínez-Fernández P;González-Castro AM;Mota-Huertas T;Arias-González L;Lucendo AJ
嗜酸性粒细胞性食管炎（EoE）中的食管微生物群和适应性免疫调节越来越多地被研究。Toll样受体（TLR）在先天免疫活性的启动和维持中起核心作用。我们的目的是描述EoE中食管和十二指肠的天然免疫应答及其通过饮食治疗的调节。食管和十二指肠活检样本收集自10名未经治疗的成人EoE，之前和之后的有效治疗与六食物消除饮食（SFED），和10名对照正常食管。在所有情况下，通过qPCR评估细菌负荷（通过16 S的mRNA表达）、TLR、粘蛋白、转录因子、白细胞介素、NKG 2D系统组分和先天免疫效应物。还通过免疫荧光测定TLR的蛋白质表达。与对照组相比，细菌负荷和TLR 1，TLR 2，TLR 4和TLR 9在具有活性EoE的活检组织中过表达。Muc 1和Muc 5 B基因表达下调，而Muc 4过表达。MyD 88和NFκB的上调与IL-1β、IL-6、IL-8和IL-10介质以及PER-1、iNOS和GRZA效应物一起被发现。NG-K2 D组分（KLRK 1、IL-15、MICB）也上调。在所有情况下，SFED和粘膜愈合后，活性EoE的变化均正常化。十二指肠样本还显示TLR-1、TLR-2和TLR-4的表达增加，但16 S或任何其他炎症介质或效应物均未增加。EoE中的食管TLR依赖性信号通路支持微生物群和先天免疫系统在这种疾病的发病机制中的潜在意义。
Esophageal microbiota and regulation of adaptive immunity are increasingly being investigated in eosinophilic esophagitis (EoE). Toll-like receptors (TLRs) play a central role in the initiation and maintenance of innate immune activity. Our objective was to characterize the esophageal and duodenal innate immune response in EoE and its modulation by dietary therapy. Esophageal and duodenal biopsy samples were collected from 10 adults with untreated EoE, before and after effective treatment with a six-food elimination diet (SFED), and 10 controls with normal esophagus. In all cases, bacterial load (by mRNA expression of 16S), TLRs, mucins, transcription factors, interleukins, components of the NKG2D system, and innate immunity effectors were assessed by qPCR. Protein expression of TLRs were also determined by immunofluorescence. Bacterial load and TLR1, TLR2, TLR4, and TLR9 were overexpressed on biopsies with active EoE compared with controls. Muc1 and Muc5B genes were downregulated while Muc4 was overexpressed. Upregulation of MyD88 and NFκB was found together with IL-1β, IL-6, IL-8, and IL-10 mediators and PER-1, iNOS, and GRZA effectors. NG-K2D components (KLRK1, IL-15, MICB) were also upregulated. In all cases, changes in active EoE were normalized following SFED and mucosal healing. Duodenal samples also showed increased expressions of TLR-1, TLR-2, and TLR-4, but not 16S or any other mediators nor effectors of inflammation. Esophageal TLR-dependent signaling pathways in EoE support the potential implication of microbiota and the innate immune system in the pathogenesis of this disease.
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影响因子：
13.6
作者：
Jiménez-Dalmaroni MJ;Gerswhin ME;Adamopoulos IE
通讯作者：
Adamopoulos IE
影响因子：
15.5
作者：
Benitez AJ;Hoffmann C;Muir AB;Dods KK;Spergel JM;Bushman FD;Wang ML
通讯作者：
Wang ML
DOI：
10.1073/pnas.1000080107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Caporaso, J. Gregory;Lauber, Christian L.;Knight, Rob
通讯作者：
Knight, Rob
影响因子：
14.2
作者：
Anto, Josep M.;Bousquet, Jean;Xu, Cheng-Jian
通讯作者：
Xu, Cheng-Jian
DOI：
10.1097/mpg.0b013e318290d15a
发表时间：
2013-07-01
影响因子：
2.9
作者：
Jensen, Elizabeth T.;Kappelman, Michael D.;Dellon, Evan S.
通讯作者：
Dellon, Evan S.