Role for Complement C5 in Eosinophilic Inflammation of Severe Asthma

作者：Cong Dong, Shaohua Lu, Zhenan Deng, Xuliang Cai, Huahao Shen, Guochao Shi, Changxing Ou, Zuofu Peng, Wei Jiang, Xiuhua Fu, Changzheng Wang, Meiling Jin, Zhongmin Qiu, Xiaoyang Wei, Wei Gu, Kewu Huang, Qiang Li, Xiangyan Zhang, Nanshan Zhong, Kian Fan Chung, Qingling Zhang · 发表于：Allergy · 年份：2025 · DOI：10.1111/all.16616 · 被引用次数：4 · 研究领域：Complement system in diseases、Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Inflammation biomarkers and pathways

BACKGROUND: We investigated the role of the complement system, particularly complement C5, in severe asthma defined from an analysis of sputum proteomics. Although there has been evidence of complement activation in asthma, its role in severe asthma remains unclear. METHOD: Sputum protein expression profiles were analyzed from healthy controls and severe asthma patients using data-dependent acquisition mass spectrometry. Weighted correlation network analysis (WGCNA) was used to define the unique modules that were highly correlated with clinical, physiologic, and inflammatory traits. Differential analysis was performed for the complement C5 pathway protein levels and eosinophilic protein expression as influenced by C5. Asthmatic mouse models were used to verify the effect of complement C5 administration and inhibition. RESULTS: The WGCNA "brown" module related to the complement system activation was positively correlated with eosinophilic inflammation. Specifically, C5 and downstream complement proteins were up-regulated in patients with high sputum eosinophil levels (≥ 3%) compared to low sputum eosinophils (< 3%). Patients with reduced C5 expression had less eosinophilic inflammation and better lung function. Using single-cell RNA sequencing and immunofluorescence staining led to identification of macrophages as the main source of C5. In vivo experiments confirmed that inhibiting C5 reduced inflammation in allergic mouse models, while direct stimulation with recombinant C5 i...