Molecular, genetic, and cellular bases for treating eosinophilic esophagitis.
Molecular, genetic, and cellular bases for treating eosinophilic esophagitis.
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DOI：
10.1053/j.gastro.2015.02.002
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发表时间：
2015-05
期刊：
影响因子：
29.4
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
Rothenberg ME
嗜酸性粒细胞性食管炎（EoE）在历史上根据组织学和对抑酸治疗缺乏反应性与胃食管反流病区分开来，但现在认识到食管嗜酸性粒细胞增多症可以对质子泵抑制剂有反应。遗传和环境因素有助于EoE的风险，特别是生命早期事件。疾病发病机制涉及上皮炎症途径的激活（产生嗜酸性粒细胞活化趋化因子-3 [由CCL 26编码]）、屏障功能受损（由桥粒芯糖蛋白-1的缺失介导）、转化生长因子-β的产生和/或活性增加以及嗜酸性粒细胞和肥大细胞诱导过敏性炎症。易感性与5 q22（TSLP）和2 p23（CAPN 14）的变异相关，表明过敏致敏和食管特异性蛋白酶途径的作用。我们认为EoE是一种独特的疾病，其特征是食物超敏反应，受早期暴露和食管特异性遗传风险变体影响的强遗传性，以及过敏性炎症，并且该疾病通过破坏炎症和辅助性T细胞2型丝氨酸介导的反应以及通过饮食消除治疗来缓解。
Eosinophilic esophagitis (EoE) was historically distinguished from gastroesophageal reflux disease on the basis of histology and lack of responsiveness to acid suppressive therapy, but it is now appreciated that esophageal eosinophilia can respond to proton pump inhibitors. Genetic and environmental factors contribute to risk for EoE—particularly early-life events. Disease pathogenesis involves activation of epithelial inflammatory pathways (production of eotaxin-3 [encoded by CCL26]), impaired barrier function (mediated by loss of desmoglein-1), increased production and/or activity of transforming growth factor-β, and induction of allergic inflammation by eosinophils and mast cells. Susceptibility has been associated with variants at 5q22 (TSLP) and 2p23 (CAPN14), indicating roles for allergic sensitization and esophageal specific protease pathways. We propose that EoE is a unique disease characterized by food hypersensitivity, strong hereditability influenced by early-life exposures and esophageal specific genetic risk variants, and allergic inflammation and that the disease is remitted by disrupting inflammatory and T-helper type 2 cytokine–mediated responses and through dietary elimination therapy.
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影响因子：
14.2
作者：
Abonia, J. Pablo;Blanchard, Carine;Butz, Bridget Buckmeier;Rainey, Heather F.;Collins, Margaret H.;Stringer, Keith;Putnam, Philip E.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
29.4
作者：
Butz BK;Wen T;Gleich GJ;Furuta GT;Spergel J;King E;Kramer RE;Collins MH;Stucke E;Mangeot C;Jackson WD;O'Gorman M;Abonia JP;Pentiuk S;Putnam PE;Rothenberg ME
通讯作者：
Rothenberg ME
影响因子：
29.4
作者：
Akei, HS;Mishra, A;Rothenberg, ME
通讯作者：
Rothenberg, ME
影响因子：
14.2
作者：
Alexander, Eileen S.;Martin, Lisa J.;Collins, Margaret H.;Kottyan, Leah C.;Sucharew, Heidi;He, Hua;Mukkada, Vincent A.;Succop, Paul A.;Abonia, J. Pablo;Foote, Heather;Eby, Michael D.;Grotjan, Tommie M.;Greenler, Alexandria J.;Dellon, Evan S.;Demain, Jeffrey G.;Furuta, Glenn T.;Gurian, Larry E.;Harley, John B.;Hopp, Russell J.;Kagalwalla, Amir;Kaul, Ajay;Nadeau, Kari C.;Noel, Richard J.;Putnam, Philip E.;von Tiehl, Karl F.;Rothenberg, Marc E.
通讯作者：
Rothenberg, Marc E.
影响因子：
158.5
作者：
Corren, Jonathan;Lemanske, Robert F., Jr.;Matthews, John G.
通讯作者：
Matthews, John G.