Clinical Immunology, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium.
Translational Research in Gastro Intestinal Disorders, KU Leuven, Leuven, Belgium.
J Allergy Clin Immunol. 2016 Apr;137(4):1043-1053.e5. doi: 10.1016/j.jaci.2015.10.050. Epub 2016 Feb 2.
Tight junction (TJ) defects have recently been associated with asthma and chronic rhinosinusitis. The expression, function, and regulation of nasal epithelial TJs remain unknown in patients with allergic rhinitis (AR).
We investigated the expression, function, and regulation of TJs in the nasal epithelium of patients with house dust mite (HDM)-induced AR and in an HDM-induced murine model of allergic airway disease.
Air-liquid interface cultures of primary nasal epithelial cells of control subjects and patients with HDM-induced AR were used for measuring transepithelial resistance and passage to fluorescein isothiocyanate-dextran 4 kDa (FD4). Ex vivo transtissue resistance and FD4 permeability of nasal mucosal explants were measured. TJ expression was evaluated by using real-time quantitative PCR and immunofluorescence. In addition, the effects of IL-4, IFN-γ, and fluticasone propionate (FP) on nasal epithelial cells were investigated in vitro. An HDM murine model was used to study the effects of allergic inflammation and FP treatment on transmucosal passage of FD4 in vivo.
A decreased resistance in vitro and ex vivo was found in patients with HDM-induced AR, with increased FD4 permeability and reduced occludin and zonula occludens-1 expression. AR symptoms correlated inversely with resistance in patients with HDM-induced AR. In vitro IL-4 decreased transepithelial resistance and increased FD4 permeability, whereas IFN-γ had no effect. FP prevented IL-4-induced barrier dysfunction in vitro. In an HDM murine model FP prevented the allergen-induced increased mucosal permeability.
We found impaired nasal epithelial barrier function in patients with HDM-induced AR, with lower occludin and zonula occludens-1 expression. IL-4 disrupted epithelial integrity in vitro, and FP restored barrier function. Better understanding of nasal barrier regulation might lead to a better understanding and treatment of AR.
紧密连接（TJ）缺陷最近与哮喘和慢性鼻-鼻窦炎有关。变应性鼻炎（AR）患者鼻上皮 TJ 的表达、功能和调节仍不清楚。
我们研究了屋尘螨（HDM）诱导的 AR 患者和 HDM 诱导的变应性气道疾病小鼠模型中鼻上皮 TJ 的表达、功能和调节。
使用对照受试者和 HDM 诱导的 AR 患者的原代鼻上皮细胞的气-液界面培养物来测量跨上皮电阻和通过荧光素异硫氰酸酯-右旋糖酐 4 kDa（FD4）的传递。测量鼻黏膜组织外的跨组织电阻和 FD4 通透性。通过实时定量 PCR 和免疫荧光评估 TJ 表达。此外，还研究了 IL-4、IFN-γ 和氟替卡松丙酸酯（FP）对鼻上皮细胞的体外作用。使用 HDM 小鼠模型研究变应性炎症和 FP 治疗对体内 FD4 跨黏膜传递的影响。
发现 HDM 诱导的 AR 患者的体外和体外阻力降低，FD4 通透性增加，occludin 和 zonula occludens-1 表达减少。HDM 诱导的 AR 患者的症状与阻力呈负相关。体外 IL-4 降低了上皮电阻并增加了 FD4 的通透性，而 IFN-γ 没有影响。FP 可防止体外 IL-4 诱导的屏障功能障碍。在 HDM 小鼠模型中，FP 可防止过敏原诱导的黏膜通透性增加。
我们发现 HDM 诱导的 AR 患者的鼻上皮屏障功能受损，occludin 和 zonula occludens-1 表达降低。IL-4 破坏了体外上皮完整性，而 FP 恢复了屏障功能。更好地了解鼻屏障调节可能会更好地理解和治疗 AR。
