Division of Ophthalmology, Department of Visual Sciences, Nihon University School of Medicine, Tokyo, Japan.
Curr Eye Res. 2021 Aug;46(8):1115-1124. doi: 10.1080/02713683.2021.1874022. Epub 2021 Jan 26.
To investigate whether crude house-dust-mite antigen exacerbates eosinophilic inflammation in the conjunctival tissues of an atopic keratoconjunctivitis mouse model in a dose-dependent manner.
An atopic keratoconjunctivitis mouse model was established by percutaneous sensitization and crude house-dust-mite antigen application in NC/Nga mice. To assess the dose-dependent response, conjunctival specimens from groups that were administered high- (High-HDM) or low-dose house-dust-mite antigen (Low-HDM) following percutaneous sensitization and the control without house-dust-mite antigen administration (control group) were evaluated. Histological examination and immunofluorescence staining were performed to determine eosinophil density and the number of IL-13-positive cells. Polymerase chain reaction array was used to obtain adaptive and innate immunity-related factor profile, and quantitative polymerase chain reaction was used to determine Il13, Il17a, Ccl11, and Ccl24 expression. Atopic keratoconjunctivitis model mice injected with anti-IL-1α antibody (IL-1α group) or vehicle (vehicle group) to the upper and lower eyelids before atopic keratoconjunctivitis development were evaluated.
Eosinophil density in the conjunctiva increased with house-dust-mite antigen application in a dose-dependent manner. CD4, CXCL10, CCR6, C3, and IL-13 mRNA levels increased more than 5-fold in the conjunctiva of the High-HDM group animals compared to those in control animals. mRNA expression of Il13 and Ccl11 in the conjunctiva of the High-HDM group animals significantly increased compared with that in the Low-HDM and control group animals. Conversely, the eosinophil density and Il13 mRNA expression significantly decreased in the IL-1α group compared with those in the vehicle group.
The house-dust-mite antigen increased eosinophilic infiltration and Il13 mRNA expression in the conjunctiva of an atopic keratoconjunctivitis mouse model in a dose-dependent manner. These inflammatory alterations were partially alleviated by eyelid injection of anti-IL-1α antibody. These findings indicate that IL-1α-induced IL-13 production constitutes a major exacerbating factor for house-dust-mite antigen-induced atopic keratoconjunctivitis.
研究粗制屋尘螨变应原是否呈剂量依赖性加重特应性角膜炎结膜炎小鼠模型的结膜组织嗜酸性粒细胞炎症。
通过皮内致敏和粗制屋尘螨抗原应用于 NC/Nga 小鼠建立特应性角膜炎结膜炎小鼠模型。为评估剂量依赖性反应，对经皮致敏后给予高剂量（High-HDM）或低剂量屋尘螨抗原（Low-HDM）的各组及未给予屋尘螨抗原的对照组（对照组）的结膜标本进行评估。进行组织学检查和免疫荧光染色以确定嗜酸性粒细胞密度和 IL-13 阳性细胞数。聚合酶链反应（PCR）阵列用于获得适应性和固有免疫相关因子谱，实时定量 PCR 用于确定 Il13、Il17a、Ccl11 和 Ccl24 的表达。在特应性角膜炎结膜炎发病前将抗 IL-1α 抗体（IL-1α 组）或载体（载体组）注入上下眼睑的特应性角膜炎结膜炎模型小鼠进行评估。
屋尘螨抗原呈剂量依赖性增加结膜中的嗜酸性粒细胞密度。与对照组相比，High-HDM 组动物结膜中的 CD4、CXCL10、CCR6、C3 和 IL-13 mRNA 水平增加了 5 倍以上。与 Low-HDM 组和对照组相比，High-HDM 组动物结膜中的 Il13 和 Ccl11 mRNA 表达显著增加。相反，与载体组相比，IL-1α 组的嗜酸性粒细胞密度和 Il13 mRNA 表达显著降低。
屋尘螨变应原呈剂量依赖性增加特应性角膜炎结膜炎小鼠模型结膜中的嗜酸性粒细胞浸润和 Il13 mRNA 表达。通过眼脸注射抗 IL-1α 抗体可部分缓解这些炎症改变。这些发现表明，IL-1α 诱导的 IL-13 产生是屋尘螨变应原诱导的特应性角膜炎结膜炎的主要加重因素。
