Gan Hui, Huang Zhifeng, Pan Qingjun, Ye Fei, Zhu Zheng, Sun Baoqing
Department of Clinical Laboratory, State Key Laboratory of Respiratory Disease, National Center for Respiratory Medicine, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Dermatology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.
Cell Commun Signal. 2025 May 6;23(1):215. doi: 10.1186/s12964-025-02220-0.
Asthma is a chronic inflammatory airway disease characterized by recurrent episodes that significantly impair disease control and reduce patients' quality of life. Despite its clinical importance, the mechanisms underlying asthma relapse remain poorly understood, and effective strategies to prevent exacerbations are still lacking.
An acute allergic asthma relapse mouse model was established using ovalbumin sensitization and challenge. Single-cell transcriptomics was employed to investigate the cellular and molecular mechanisms driving asthma relapse. Flow cytometry and gene knockout experiments were conducted to validate the findings.
We successfully established an acute allergic asthma relapse mouse model. Single-cell transcriptomic analysis revealed that T cells and type 2 innate lymphoid cells (ILC2s) are pivotal during asthma relapse, serving as the primary cellular sources of type 2 inflammatory cytokines. Further subcluster analysis identified T-cell subcluster 4 and ILC2 subcluster 0 as the predominant contributors to type 2 cytokine production. Complex intercellular communication networks were observed, with macrophages, natural killer (NK) cells, and dendritic cells functioning as central signaling hubs. Pseudo-time trajectory analysis highlighted the critical role of ILC2s and the Il1rl1 signaling pathway in asthma relapse. These findings were corroborated by flow cytometry. Il1rl1-deficient mice displayed similar pulmonary inflammation to wild-type mice during the initial asthma episode; however, asthma relapse was significantly attenuated. Mechanistically, Il1rl1 deficiency resulted in a substantial reduction in both the number and functional capacity of ILC2s.
The recurrence of acute allergic asthma is driven, at least in part, by ILC2s through Il1rl1 signaling. Genetic ablation of Il1rl1 significantly suppresses asthma relapse, suggesting that targeting Il1rl1 may represent a novel therapeutic strategy for preventing asthma exacerbations.
哮喘是一种慢性炎症性气道疾病，其特征为反复发作，严重影响疾病控制并降低患者生活质量。尽管哮喘具有临床重要性，但其复发的潜在机制仍知之甚少，且仍缺乏预防病情加重的有效策略。
通过卵清蛋白致敏和激发建立急性过敏性哮喘复发小鼠模型。采用单细胞转录组学研究驱动哮喘复发的细胞和分子机制。进行流式细胞术和基因敲除实验以验证研究结果。
我们成功建立了急性过敏性哮喘复发小鼠模型。单细胞转录组分析显示，T细胞和2型固有淋巴细胞（ILC2s）在哮喘复发过程中起关键作用，是2型炎症细胞因子的主要细胞来源。进一步的亚群分析确定T细胞亚群4和ILC2亚群0是2型细胞因子产生的主要贡献者。观察到复杂的细胞间通讯网络，巨噬细胞、自然杀伤（NK）细胞和树突状细胞作为中心信号枢纽发挥作用。伪时间轨迹分析突出了ILC2s和Il1rl1信号通路在哮喘复发中的关键作用。这些发现通过流式细胞术得到了证实。Il1rl1缺陷小鼠在初始哮喘发作期间表现出与野生型小鼠相似的肺部炎症；然而，哮喘复发明显减轻。从机制上讲，Il1rl1缺陷导致ILC2s的数量和功能能力大幅降低。
急性过敏性哮喘的复发至少部分由ILC2s通过Il1rl1信号驱动。Il1rl1的基因消融显著抑制哮喘复发，这表明靶向Il1rl1可能代表一种预防哮喘病情加重的新治疗策略。
