Shuochuan Shi, Jintao Zhang, Yun Pan, Xiaofei Liu, Rong Zeng, Changjuan Xu, Ying Wang, Qian Qi, Zhi Guo, Chengfang Yao, Ju Liu, Jianwen Fei, Li Li, Liang Dong
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引用次数: 0
Abstract
Purpose: Airway inflammation and remodeling are pivotal in asthma pathogenesis. Interleukin-17D (IL-17D), a recently characterized cytokine within the IL-17 family, is found to be expressed at higher levels in lung tissue; however, its role in asthma remains unclear. This study aims to elucidate the function and mechanisms of IL-17D in asthma, providing new insights for therapeutic strategies.
Methods: We analyzed IL-17D messenger RNA expression levels using datasets from the Gene Expression Omnibus (GEO). Bronchoscopic biopsy tissues and serum samples from asthmatics, along with lung tissues from chronic asthmatic mice, were collected to validate IL-17D expression. Lentivirus-mediated IL-17D knockdown was performed in a chronic asthma mouse model induced by ovalbumin (OVA). Recombinant murine IL-17D protein was intranasally administered to further investigate its impact. In vitro, human bronchial epithelial cells (16HBE) were treated with recombinant human IL-17D or CD93-targeting small interfering RNA to explore signaling mechanisms.
Results: GEO data and experimental findings revealed that IL-17D expression was reduced in the airway epithelia of asthmatics and chronic asthmatic mice. In vivo, knockdown of IL-17D exacerbated peri-airway inflammation and promoted epithelial-mesenchymal transition (EMT) in OVA-induced asthmatic mice. Conversely, recombinant IL-17D protein administration significantly attenuated airway inflammation, extracellular matrix (ECM) deposition, and EMT progression. In vitro, IL-17D mitigated transforming growth factor-β1-induced fibrotic remodeling in 16HBE cells, with CD93 receptor silencing partially reversing these effects.
Conclusions: Our findings suggest that IL-17D could play a protective role in asthmatic airway inflammation and remodeling, partially through the CD93 receptors. These results highlight IL-17D as a potential therapeutic target for asthma management.
期刊介绍：
The journal features cutting-edge original research, brief communications, and state-of-the-art reviews in the specialties of allergy, asthma, and immunology, including clinical and experimental studies and instructive case reports. Contemporary reviews summarize information on topics for researchers and physicians in the fields of allergy and immunology. As of January 2017, AAIR do not accept case reports. However, if it is a clinically important case, authors can submit it in the form of letter to the Editor. Editorials and letters to the Editor explore controversial issues and encourage further discussion among physicians dealing with allergy, immunology, pediatric respirology, and related medical fields. AAIR also features topics in practice and management and recent advances in equipment and techniques for clinicians concerned with clinical manifestations of allergies and pediatric respiratory diseases.
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