Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis
Eotaxin-3 and a uniquely conserved gene-expression profile in eosinophilic esophagitis
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DOI：
10.1172/jci26679
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发表时间：
2006-02-01
影响因子：
15.9
通讯作者：
Rothenberg, ME
中科院分区：
文献类型：
--
作者：
Blanchard, C;Wang, N;Rothenberg, ME
嗜酸性粒细胞性食管炎（EE）是一种新出现的疾病，发病机制尚不清楚。为了明确疾病机制，我们采用了一种经验方法，通过全基因组微阵列表达分析来分析食管组织。情感表达患者有一个惊人的转录特征，涉及人类基因组的1%，在性别、年龄和过敏状态方面都非常保守，与非情感表达慢性食管炎相关的转录特征不同。值得注意的是，与健康个体的表达水平相比，编码嗜酸性粒细胞特异性趋化剂eotaxin-3（也称为CCL26）的基因在EE患者中是诱导程度最高的基因。食管eotaxin-3 mRNA和蛋白水平与组织嗜酸性粒细胞增多和肥大细胞增多密切相关。此外，人类eotaxin-3基因的单核苷酸多态性与疾病易感性相关。最后，eotaxin受体（也称为CCR3）缺乏的小鼠受到实验性EE的保护。这些结果暗示eotaxin-3是EE的关键效应分子，并为疾病发病机制提供了见解。
Eosinophilic esophagitis (EE) is an emerging disorder with a poorly understood pathogenesis. In order to, define disease mechanisms, we took an empirical approach analyzing esophageal tissue by a genome-wide microarray expression analysis. EE patients had a striking transcript signature involving 1% of the human genome that was remarkably conserved across sex, age, and allergic status and was distinct from that associated with non-EE chronic esophagitis. Notably, the gene encoding the eosinophil-specific chemoattractant eotaxin-3 (also known as CCL26) was the most highly induced gene in EE patients compared with its expression level in healthy individuals. Esophageal eotaxin-3 mRNA and protein levels strongly correlated with tissue eosinophilia and mastocytosis. Furthermore, a single-nucleotide polymorphism in the human eotaxin-3 gene was associated with disease susceptibility. Finally, mice deficient in the eotaxin receptor (also known as CCR3) were protected from experimental EE. These results implicate eotaxin-3 as a critical effector molecule for EE and provide insight into disease pathogenesis.