GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases

作者：Feng Lan, Jizhou Li, Wenxuan Miao, Fei Sun, Su Duan, Yabing Song, Jiacheng Yao, Xiangdong Wang, Chengshuo Wang, Xin Liu, Jianbin Wang, Luo Zhang, Hai Qi · 发表于：Nature · 年份：2025 · DOI：10.1038/s41586-024-08395-9 · 被引用次数：111 · 研究领域：Asthma and respiratory diseases、Allergic Rhinitis and Sensitization、Sinusitis and nasal conditions

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory diseases such as psoriasis2, Crohn’s disease3, oesophagitis4 and multiple sclerosis5,6, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7. Chronic rhinosinusitis affects more than 10% of the general population8. Among these patients, 20–25% would develop nasal polyps, which often require repeated surgical resections owing to a high incidence of recurrence9. Whereas abundant T cells infiltrate the nasal polyps tissue10,11, T cell subsets that drive the disease pathology and promote recurrence are not fully understood. By comparing T cell repertoires in nasal polyp tissues obtained from consecutive surgeries, here we report that persistent CD8+ T cell clones carrying effector memory-like features colonize the mucosal tissue during disease recurrence, and these cells characteristically express the tryptase Granzyme K (GZMK). We find that GZMK cleaves many complement components, including C2, C3, C4 and C5, that collectively contribute to the activation of the complement cascade. GZMK-expressing CD8+ T cells participate in organized tertiary lymphoid structures, and tissue GZMK levels predict the dise...