哮喘中气道上皮衍生警报素的调节：治疗靶点的展望
2024/10/29
摘要
哮喘是主要由2型免疫反应驱动的慢性呼吸系统疾病。上皮来源的警报素如胸腺基质淋巴细胞生成素（TSLP）、白细胞介素(IL)-33和IL-25与其他免疫效应细胞一起协调下游Th2细胞和2组固有淋巴样细胞（ILC2s）的活化。虽然这些警报素是对吸入触发物（如变应原、呼吸道病原体或颗粒物）做出反应而产生，但气道上皮细胞不成比例地产生警报素可导致哮喘加重。由于警报素在2型炎症级联的上游产生，了解这些警报素的调节和表达通路对于进一步探索哮喘患者的治疗新疗法至关重要。本综述强调了气道上皮和上皮源性警报素在哮喘发病机制中的关键作用，并强调了靶向警报素作为改善哮喘患者预后的潜在治疗手段的潜力。
Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets
Ravneet K Hansi, Maral Ranjbar, Christiane E Whetstone, Gail M Gauvreau
Abstract
Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients.
哮喘是主要由2型免疫反应驱动的慢性呼吸系统疾病。上皮来源的警报素如胸腺基质淋巴细胞生成素（TSLP）、白细胞介素(IL)-33和IL-25与其他免疫效应细胞一起协调下游Th2细胞和2组固有淋巴样细胞（ILC2s）的活化。虽然这些警报素是对吸入触发物（如变应原、呼吸道病原体或颗粒物）做出反应而产生，但气道上皮细胞不成比例地产生警报素可导致哮喘加重。由于警报素在2型炎症级联的上游产生，了解这些警报素的调节和表达通路对于进一步探索哮喘患者的治疗新疗法至关重要。本综述强调了气道上皮和上皮源性警报素在哮喘发病机制中的关键作用，并强调了靶向警报素作为改善哮喘患者预后的潜在治疗手段的潜力。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Biomedicines. 2024 Oct 11;12(10):2312. doi: 10.3390/biomedicines12102312.)
(Biomedicines. 2024 Oct 11;12(10):2312. doi: 10.3390/biomedicines12102312.)
Regulation of Airway Epithelial-Derived Alarmins in Asthma: Perspectives for Therapeutic Targets
Ravneet K Hansi, Maral Ranjbar, Christiane E Whetstone, Gail M Gauvreau
Abstract
Asthma is a chronic respiratory condition predominantly driven by a type 2 immune response. Epithelial-derived alarmins such as thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, and IL-25 orchestrate the activation of downstream Th2 cells and group 2 innate lymphoid cells (ILC2s), along with other immune effector cells. While these alarmins are produced in response to inhaled triggers, such as allergens, respiratory pathogens or particulate matter, disproportionate alarmin production by airway epithelial cells can lead to asthma exacerbations. With alarmins produced upstream of the type 2 inflammatory cascade, understanding the pathways by which these alarmins are regulated and expressed is critical to further explore new therapeutics for the treatment of asthmatic patients. This review emphasizes the critical role of airway epithelium and epithelial-derived alarmins in asthma pathogenesis and highlights the potential of targeting alarmins as a promising therapeutic to improve outcomes for asthma patients.
上一篇：
杨梅素通过激活Sirt1调节JNK/Smad3通路改善哮喘气道炎症和重塑
下一篇：
高CBD提取物（CBD-X）在哮喘管理中的作用：降低Th2驱动的细胞因子分泌和中性粒细胞/嗜酸性粒细胞活性
