Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, 45229-3039, USA.
Sci Rep. 2017 Dec 14;7(1):17563. doi: 10.1038/s41598-017-17541-5.
The molecular and cellular etiology of eosinophilic esophagitis (EoE), an emerging tissue-specific allergic disease, involves dysregulated gene expression in esophageal epithelial cells. Herein, we assessed the esophageal expression of IL-33, an epithelium-derived alarmin cytokine, in patients with EoE. IL-33 protein was markedly overexpressed within the nuclei of a subpopulation of basal layer esophageal epithelial cells in patients with active EoE compared to control individuals. IL-33 exhibited dynamic expression as levels normalized upon EoE remission. IL-33-positive basal epithelial cells expressed E-cadherin and the undifferentiated epithelial cell markers keratin 5 and 14 but not the differentiation marker keratin 4. Moreover, the IL-33-positive epithelial cells expressed the epithelial progenitor markers p75 and p63 and lacked the proliferation markers Ki67 and phospho-histone H3. Additionally, the IL-33-positive cells had low expression of PCNA. IL-33 expression was detected in ex vivo-cultured primary esophageal epithelial cells in a subpopulation of cells lacking expression of proliferation markers. Collectively, we report that IL-33 expression is induced in an undifferentiated, non-dividing esophageal epithelial cell population in patients with active EoE.
嗜酸粒细胞性食管炎（EoE）是一种新兴的组织特异性过敏疾病，其分子和细胞病因涉及食管上皮细胞中基因表达的失调。在此，我们评估了 IL-33 在 EoE 患者中的食管表达。与对照组相比，活动期 EoE 患者的食管基底细胞层亚群中，IL-33 蛋白在细胞核中明显过表达。EoE 缓解时，IL-33 水平正常化。IL-33 阳性基底上皮细胞表达 E-钙黏蛋白和未分化的上皮细胞标志物角蛋白 5 和 14，但不表达分化标志物角蛋白 4。此外，IL-33 阳性上皮细胞表达上皮祖细胞标志物 p75 和 p63，缺乏增殖标志物 Ki67 和磷酸化组蛋白 H3。此外，IL-33 阳性细胞的 PCNA 表达水平较低。在体外培养的原发性食管上皮细胞中，我们检测到了亚群细胞缺乏增殖标志物的 IL-33 表达。综上所述，我们报告在活动期 EoE 患者中，IL-33 表达于未分化、不分裂的食管上皮细胞群体中。
