Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling
Abstract Background 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 st...
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BMC
2025-05-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02220-0 |
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| author | Hui Gan Zhifeng Huang Qingjun Pan Fei Ye Zheng Zhu Baoqing Sun |
| author_facet | Hui Gan Zhifeng Huang Qingjun Pan Fei Ye Zheng Zhu Baoqing Sun |
| author_sort | Hui Gan |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusion 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. |
| format | Article |
| id | doaj-art-c18665ed790e4e3ba7cc858cc0cc0376 |
| institution | DOAJ |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-c18665ed790e4e3ba7cc858cc0cc03762025-08-20T03:09:19ZengBMCCell Communication and Signaling1478-811X2025-05-0123111710.1186/s12964-025-02220-0Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signalingHui Gan0Zhifeng Huang1Qingjun Pan2Fei Ye3Zheng Zhu4Baoqing Sun5Department 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 UniversityDepartment 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 UniversityDepartment 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 UniversityAllergy Department/Otolaryngology Head and Neck Surgery, Department of Zhongshan People’s HospitalDepartment 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 UniversityDepartment 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 UniversityAbstract Background 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. Methods 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. Results 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. Conclusion 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.https://doi.org/10.1186/s12964-025-02220-0AsthmaRelapseSingle-cell transcriptomicsILC2Il1rl1 |
| spellingShingle | Hui Gan Zhifeng Huang Qingjun Pan Fei Ye Zheng Zhu Baoqing Sun Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling Cell Communication and Signaling Asthma Relapse Single-cell transcriptomics ILC2 Il1rl1 |
| title | Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling |
| title_full | Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling |
| title_fullStr | Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling |
| title_full_unstemmed | Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling |
| title_short | Recurrence of acute allergic asthma depends on the role of ILC2 driven by Il1rl1 signaling |
| title_sort | recurrence of acute allergic asthma depends on the role of ilc2 driven by il1rl1 signaling |
| topic | Asthma Relapse Single-cell transcriptomics ILC2 Il1rl1 |
| url | https://doi.org/10.1186/s12964-025-02220-0 |
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