Li Yan, Wang Wei, Huang Ping, Zhang Qian, Yao Xiujuan, Wang Jingjing, Lv Zhe, An Yunqing, Corrigan Chris J, Huang Kewu, Ying Sun
The Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University & Beijing Institute of Respiratory Medicine, Beijing, China.
The Department of Immunology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Immunology. 2015 Aug;145(4):508-18. doi: 10.1111/imm.12465. Epub 2015 May 17.
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 hyper-responsiveness, 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.
白细胞介素-25（IL-25）和IL-33属于不同的细胞因子家族，可诱导并促进2型辅助性T细胞介导的气道炎症。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功能之间的差异以及它们如何导致不同的疾病“内型”。为了解决这一问题，我们在已建立的小鼠哮喘模型中，通过经鼻直接气道激发，对IL-25和IL-33对气道炎症和生理学的影响进行了直接比较。用IL-33或IL-25进行鼻内激发可诱导炎性细胞浸润、胶原蛋白沉积、气道平滑肌肥大、血管生成和气道高反应性，但均未增加全身IgE或IgG1的产生。与IL-25相比，IL-33诱导的反应的特征是细胞外基质蛋白的持续沉积、新生血管生成、2型辅助性T细胞细胞因子表达以及组织阻尼升高。因此，在考虑人类疾病治疗的分子靶点时，IL-25和IL-33可能都对哮喘“内型”有显著且独立的作用。
