Institute of Allergy and Clinical Immunology, Medical Research Center, Seoul National University, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea.
Division of Allergy and Clinical Immunology, Department of Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Republic of Korea.
J Mol Med (Berl). 2019 Jul;97(7):937-949. doi: 10.1007/s00109-019-01768-y. Epub 2019 Apr 24.
It has been recently reported that cigarette smoke exposure during allergen sensitization facilitates the development of allergic asthma; however, the underlying mechanisms remain elusive. We evaluated the role of interleukin (IL-23) in a cigarette smoke extract (CSE)-induced Dermatophagoides pteronyssinus (Dp)-allergic asthma mouse model. BALB/c mice were exposed to CSE during allergen sensitization period. Anti-IL-23p19 or IL-23R antibody was administered during the sensitization period. And we evaluated several immunological responses. The expression of IL-23 and IL-23 receptor (IL-23R) was examined in lung tissue. IL-23 and IL-23R expression was increased in the airway epithelium of Dp/CSE co-administered mice. CSE administration during the sensitization promoted Dp-allergic sensitization and the development of asthma phenotypes. Additionally, the proportion of innate lymphoid type 2 cells (ILC2) was also increased by CSE and Dp co-instillation. Anti-IL-23 or IL-23R antibody treatment during allergen sensitization significantly diminished phenotypes of allergic asthma and the ILC2 population. The levels of IL-33 and thymic stromal lymphopoietin (TSLP) were also significantly reduced by anti-IL-23 or IL-23R antibody treatment. IL-23 may thus play a significant role in cigarette smoke-induced allergic sensitization and asthma development. Clinically, the increase in allergen sensitization due to cigarette exposure causes onset of asthma, and IL-23 may be important in this mechanism. KEY MESSAGES: IL-23 and IL-23R expression was increased in the lung epithelium of Dp and CSE co-exposed mice during sensitization period. The population of ILC2s was increased in Dp and CSE co-exposed mice during sensitization period. Anti-IL23 or IL-23R antibody treatment with co-administration of CSE and HDM during sensitization period significantly suppresses ILC2. In vitro, IL-23 blockade in Dp and CSE-stimulated epithelial cells suppressed IL-13 expression in ILC2.
最近有报道称，在变应原致敏期间暴露于香烟烟雾会促进过敏性哮喘的发展；然而，其潜在机制仍难以捉摸。我们评估了白细胞介素（IL-23）在香烟烟雾提取物（CSE）诱导的屋尘螨（Dp）变应原性哮喘小鼠模型中的作用。BALB/c 小鼠在致敏期间暴露于 CSE 中。在致敏期间给予抗 IL-23p19 或 IL-23R 抗体。并评估了几种免疫反应。检查肺组织中 IL-23 和 IL-23 受体（IL-23R）的表达。在 Dp/CSE 共同给药小鼠的气道上皮中观察到 IL-23 和 IL-23R 的表达增加。在致敏期间给予 CSE 促进 Dp 变应原致敏和哮喘表型的发展。此外，CSE 和 Dp 共同注入也增加了先天淋巴样细胞 2 型（ILC2）的比例。在变应原致敏期间给予抗 IL-23 或 IL-23R 抗体治疗可显著减轻过敏性哮喘和 ILC2 群体的表型。IL-33 和胸腺基质淋巴细胞生成素（TSLP）的水平也通过抗 IL-23 或 IL-23R 抗体治疗显著降低。因此，IL-23 可能在香烟烟雾诱导的变应原致敏和哮喘发展中发挥重要作用。临床上，由于香烟暴露导致变应原致敏增加，从而引发哮喘，而 IL-23 可能在这种机制中起重要作用。关键信息：在致敏期间，Dp 和 CSE 共同暴露的小鼠肺上皮中 IL-23 和 IL-23R 的表达增加。在致敏期间，Dp 和 CSE 共同暴露的小鼠中 ILC2 的数量增加。在致敏期间给予 CSE 和 HDM 共同给药时，抗 IL-23 或 IL-23R 抗体治疗可显著抑制 ILC2。在体外，在 Dp 和 CSE 刺激的上皮细胞中阻断 IL-23 可抑制 ILC2 中的 IL-13 表达。
