Liu Yang, Fu Li, Liu Zheng
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Institute of Allergy and Clinical Immunology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Clin Med. 2023 Mar 22;12(6):2433. doi: 10.3390/jcm12062433.
The airway epithelium is exposed to numerous external irritants including infectious agents, environmental allergens, and atmospheric pollutants, releasing epithelial cytokines including thymic stromal lymphopoietin (TSLP), IL-33, and IL-25 and initiating downstream type 2 (IL-4, IL-13, and IL-5) and IgE-driven pathways. These pathways trigger the initiation and progression of allergic airway diseases, including chronic rhinosinusitis with nasal polyps (CRSwNP), allergic rhinitis (AR), and allergic asthma. However, the use of biological agents that target downstream cytokines, such as IL-5, IL-4, and IL-13 receptors and IgE, might not be sufficient to manage some patients successfully. Instead of blocking downstream cytokines, targeting upstream epithelial cytokines has been proposed to address the complex immunologic networks associated with allergic airway diseases. Osteopontin (OPN), an extracellular matrix glyco-phosphoprotein, is a key mediator involved in Th1-related diseases, including systemic lupus erythematosus, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. Emerging evidence, including ours, indicates that epithelial-cell-derived OPN also plays an essential role in Th2-skewed airway diseases, including CRSwNP, AR, and allergic asthma involving the Th17 response. Therefore, we reviewed the current knowledge of epithelial-cell-derived OPN in the pathogenesis of three type-2-biased airway diseases and provided a direction for its future investigation and clinical relevance.
气道上皮暴露于多种外部刺激物，包括感染因子、环境过敏原和大气污染物，释放包括胸腺基质淋巴细胞生成素（TSLP）、白细胞介素-33（IL-33）和白细胞介素-25（IL-25）在内的上皮细胞因子，并启动下游2型（白细胞介素-4、白细胞介素-13和白细胞介素-5）和免疫球蛋白E（IgE）驱动的途径。这些途径引发过敏性气道疾病的发生和发展，包括伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）、过敏性鼻炎（AR）和过敏性哮喘。然而，使用靶向下游细胞因子（如白细胞介素-5、白细胞介素-4和白细胞介素-13受体以及IgE）的生物制剂可能不足以成功治疗某些患者。为了解决与过敏性气道疾病相关的复杂免疫网络问题，有人提出靶向上游上皮细胞因子，而不是阻断下游细胞因子。骨桥蛋白（OPN）是一种细胞外基质糖磷蛋白，是参与1型辅助性T细胞（Th1）相关疾病（包括系统性红斑狼疮、多发性硬化症、炎症性肠病和类风湿性关节炎）的关键介质。包括我们的研究在内的新证据表明，上皮细胞来源的OPN在2型偏向性气道疾病（包括CRSwNP、AR和涉及Th17反应的过敏性哮喘）的发病机制中也起着重要作用。因此，我们综述了目前关于上皮细胞来源的OPN在三种2型偏向性气道疾病发病机制中的认识，并为其未来的研究和临床相关性提供了方向。
