Distinct sustained structural and functional effects of interleukin-33 and interleukin-25 on the airways in a murine asthma surrogate
Distinct sustained structural and functional effects of interleukin-33 and interleukin-25 on the airways in a murine asthma surrogate
复制标题
白细胞介素 33 和白细胞介素 25 对小鼠哮喘替代物气道的独特持续结构和功能影响
DOI：
10.1111/imm.12465
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发表时间：
2015-08-01
期刊：
影响因子：
6.4
通讯作者：
Ying, Sun
中科院分区：
文献类型：
--
作者：
Li, Yan;Wang, Wei;Ying, Sun
白介素 25 (IL-25) 和 IL-33 属于不同的细胞因子家族，可诱导和促进 2 型辅助性 T 气道炎症。这两种细胞因子可能在哮喘中发挥作用，但缺乏直接证据来阐明它们的功能之间的区别以及它们如何导致不同的疾病“内型”。为了解决这个问题，我们在我们建立的小鼠哮喘替代物中直接比较了 IL-25 和 IL-33 对气道炎症和生理学的影响，其中涉及经鼻直接气道激发。 IL-33 或 IL-25 鼻内攻击诱导炎症细胞浸润、胶原沉积、气道平滑肌肥大、血管生成和气道高反应性，但均不增加 IgE 或 IgG1 的全身产生。与IL-25相比，IL-33诱导的反应的特点是更持久地沉积细胞外基质蛋白、新血管生成、T辅助细胞2型细胞因子表达和组织阻尼升高。因此，在考虑治疗人类疾病的分子靶标时，IL-25 和 IL-33 可能对哮喘“内型”有显着且独立的贡献。
Interleukin-25 (IL-25) and IL-33, which belong to distinct cytokine families, induce and promote T helper type 2 airway inflammation. Both cytokines probably play a role in asthma, but there is a lack of direct evidence to clarify distinctions between their functions and how they might contribute to distinct 'endotypes' of disease. To address this, we made a direct comparison of the effects of IL-25 and IL-33 on airway inflammation and physiology in our established murine asthma surrogate, which involves per-nasal, direct airway challenge. Intranasal challenge with IL-33 or IL-25 induced inflammatory cellular infiltration, collagen deposition, airway smooth muscle hypertrophy, angiogenesis and airway hyperresponsiveness, but neither increased systemic production of IgE or IgG1. Compared with that of IL-25, the IL-33-induced response was characterized by more sustained laying down of extracellular matrix protein, neoangiogenesis, T helper type 2 cytokine expression and elevation of tissue damping. Hence, both IL-25 and IL-33 may contribute significantly and independently to asthma 'endotypes' when considering molecular targets for the treatment of human disease.