Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.
Interleukin 9 Alters Epithelial Barrier and E-cadherin in Eosinophilic Esophagitis.
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DOI：
10.1097/mpg.0000000000002144
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发表时间：
2019-03
影响因子：
2.9
通讯作者：
Aceves SS
中科院分区：
文献类型：
--
作者：
Doshi A;Khamishon R;Rawson R;Duong L;Dohil L;Myers SJ;Bell B;Dohil R;Newbury RO;Barrett KE;Kurten RC;Aceves SS
嗜酸性粒细胞性食管炎 (EoE) 是一种与 Th2 相关的慢性炎症，伴有上皮屏障功能严重受损和表达 IL-9 的炎症细胞数量增加。虽然已知 IL-9 会影响肠道屏障功能，但 IL-9 对食道的功能影响尚不清楚。在此，我们旨在了解 EoE 中 IL-9 受体的表达以及 IL-9 对上皮的影响。我们使用患有活动性和非活动性疾病的儿科 EoE 患者的食管活检来分析 IL-9 受体、粘附连接蛋白 E-钙粘蛋白和紧密连接蛋白claudin-1 的表达。我们用 IL-9 处理原代人食管上皮细胞，以了解其对 E-钙粘蛋白表达和功能的影响。活跃的 EoE 受试者的 IL-9 受体 mRNA 和蛋白的上皮表达增加 (p<0.05)，膜结合 E-钙粘蛋白 (p<0.01) 和 Claudin-1 (p<0.05) 表达减少。 IL-9受体表达和错位claudin-1呈正相关，而膜结合E-钙粘蛋白表达与组织学上皮重塑程度呈负相关(p<0.05)。 IL-9 降低分层原代人食管上皮细胞中的上皮抵抗力（p<0.01）和上皮细胞单层中的膜结合 E-钙粘蛋白（p<0.01）。这些数据表明 IL-9、其受体及其对 E-钙粘蛋白的影响可能是 EoE 中上皮屏障破坏的重要机制。
Eosinophilic esophagitis (EoE) is a chronic Th2-assocated inflammatory condition accompanied by substantial impairments in epithelial barrier function and increased numbers of IL-9 expressing inflammatory cells. While IL-9 is known to affect barrier function in the intestine, the functional effects of IL-9 on the esophagus are unclear. Herein we aimed to understand the expression of the IL-9 receptor and effects of IL-9 on the epithelium in EoE. We used esophageal biopsies from pediatric EoE patients with active and inactive disease to analyze the expression of the IL-9 receptor, the adherens junction protein E-cadherin and the tight junction protein claudin-1. We treated primary human esophageal epithelial cells with IL-9 to understand its effects on E-cadherin expression and function. Active EoE subjects had increased epithelial expression of IL-9 receptor mRNA and protein (p<0.05) and decreased membrane bound E-cadherin (p<0.01) and claudin-1 (p<0.05) expression. IL-9 receptor expression and mislocalized claudin-1 positively correlated and while membrane bound E-cadherin expression negatively correlated with the degree of histologic epithelial remodeling (p<0.05). IL-9 decreased epithelial resistance in stratified primary human esophageal epithelial cells (p<0.01) and membrane bound E-cadherin in epithelial cell monolayers (p<0.01). These data suggest that IL-9, its receptor, and its effects on E-cadherin may be important mechanisms for epithelial barrier disruption in EoE.