Department of Otolaryngology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Mediators Inflamm. 2021 Apr 23;2021:6694109. doi: 10.1155/2021/6694109. eCollection 2021.
Allergic rhinitis (AR) affects millions of people and is lack of effective treatment. CD40 is an important costimulatory molecule in immunity. However, few studies have focused on the role of CD40 in AR.
In this study, we built mouse model of chronic AR. The mice were divided into the AR, control, intravenous CD40 siRNA, and nasal CD40 siRNA groups ( = 6 each). We detected OVA-sIgE, IL-4, IL-5, IL-13, IL-10, IFN-, and TGF- levels in serum and supernatant by ELISA, CD40 splenic DCs, and Foxp3 Tregs by flow cytometry and CD40 mRNA by RT-PCR. We also used PAS and MT stains to assess tissue remodelling.
(1) The OVA-sIgE, IL-4, IL-5, and IL-13 levels in the serum or supernatant of nasal septal membrane of AR mice were significantly higher than control. After treated with CD40 siRNA, those indicators were significantly decreased. The IFN-, IL-10, and TGF- levels in AR mice were significantly lower than that in control and were increased by administration of CD40 siRNA. (2) AR mice had significantly fewer Foxp3 Tregs in the spleen than control mice. After treated with CD40 siRNA, AR mice had significantly more Foxp3 Tregs. (3) AR mice exhibited a significantly higher CD40 mRNA levels than control. Administration of CD40 siRNA significantly reduced the CD40 mRNA level. (4) The AR mice showed significantly greater collagen deposition than the control in MT staining. Applications of CD40 siRNA significantly reduced the collagen deposition in AR mice.
CD40 siRNA therapy shows promise for chronic AR as it significantly attenuated allergic symptoms and Th2-related inflammation and upregulated Foxp3 Tregs. CD40 plays a role in tissue remodelling in AR, which can be inhibited by CD40 siRNA application.
变应性鼻炎（AR）影响着数百万人，且缺乏有效的治疗方法。CD40 是免疫中一种重要的共刺激分子。然而，很少有研究关注 CD40 在 AR 中的作用。
本研究构建了慢性 AR 小鼠模型。将小鼠分为 AR 组、对照组、静脉注射 CD40 siRNA 组和鼻内 CD40 siRNA 组（每组 6 只）。通过 ELISA 检测血清和上清液中 OVA-sIgE、IL-4、IL-5、IL-13、IL-10、IFN-γ和 TGF-β水平，流式细胞术检测脾 CD40 树突状细胞（DCs）和 Foxp3 T 调节细胞（Tregs），RT-PCR 检测 CD40 mRNA。PAS 和 MT 染色评估组织重塑。
（1）AR 小鼠血清或鼻中隔鼻黏膜上清液中 OVA-sIgE、IL-4、IL-5 和 IL-13 水平明显高于对照组，经 CD40 siRNA 治疗后明显降低。AR 小鼠 IFN-γ、IL-10 和 TGF-β水平明显低于对照组，经 CD40 siRNA 治疗后升高。（2）与对照组相比，AR 小鼠脾脏中 Foxp3 Tregs 明显减少，经 CD40 siRNA 治疗后 Foxp3 Tregs 明显增多。（3）与对照组相比，AR 小鼠 CD40 mRNA 水平明显升高，经 CD40 siRNA 治疗后 CD40 mRNA 水平明显降低。（4）MT 染色显示，AR 小鼠胶原沉积明显多于对照组，经 CD40 siRNA 治疗后 AR 小鼠胶原沉积明显减少。
CD40 siRNA 治疗可显著减轻变应性症状和 Th2 相关炎症，上调 Foxp3 Tregs，对慢性 AR 有一定疗效。CD40 参与 AR 组织重塑，CD40 siRNA 应用可抑制其作用。
