TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases
Abstract Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that to...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62532-0 |
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| author | Yan Li Zaichuan Wang Su Duan Xue Wang Yuling Zhang Claus Bachert Nan Zhang Wei Wang Sun Ying Feng Lan Chengshuo Wang Luo Zhang |
| author_facet | Yan Li Zaichuan Wang Su Duan Xue Wang Yuling Zhang Claus Bachert Nan Zhang Wei Wang Sun Ying Feng Lan Chengshuo Wang Luo Zhang |
| author_sort | Yan Li |
| collection | DOAJ |
| description | Abstract Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that toll-like receptor 4 (TLR4)+ILC2s, with similar markers to their human counterparts, expresse memory cell markers, persist over time, and respond more vigorously to a secondary unrelated antigen challenge in the mouse model. Genetic ablation of TLR4 or blockade by anti-TLR4 antibodies leads to the reduction of IL-13 expression from ILC2s and mucus production in mice. The assay for transposase-accessible chromatin sequencing further confirms the importance of accessible TLR4 gene loci and its down-stream signaling pathway in maintaining trained immunity of TLR4+ILC2s after repeated stimulation by HDM. Taken together, TLR4 has a function in trained immunity maintenance within ILC2s, which may contribute to disease chronicity through a non-specific immunological memory. |
| format | Article |
| id | doaj-art-914e4aa5bd7e43d9a4613eca0e2bedbe |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-914e4aa5bd7e43d9a4613eca0e2bedbe2025-08-20T04:03:00ZengNature PortfolioNature Communications2041-17232025-08-0116111710.1038/s41467-025-62532-0TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseasesYan Li0Zaichuan Wang1Su Duan2Xue Wang3Yuling Zhang4Claus Bachert5Nan Zhang6Wei Wang7Sun Ying8Feng Lan9Chengshuo Wang10Luo Zhang11Beijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseDepartment of Otorhinolaryngology Head and Neck Surgery, University Hospital of MünsterUpper Airways Research Laboratory, ENT Department, Ghent UniversityDepartment of Immunology, School of Basic Medical Sciences, Capital Medical UniversityDepartment of Immunology, School of Basic Medical Sciences, Capital Medical UniversityBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseBeijing Institute of Otolaryngology, Beijing Laboratory of Allergic Diseases, Beijing Key Laboratory of New Medicine and Diagnostic Technology Research for Nasal DiseaseAbstract Group 2 innate lymphoid cells (ILC2s) directly contribute to local inflammation in type 2 inflammatory airway diseases. Here, we identify ILC2 subsets by single cell RNA sequencing in chronic rhinosinusitis with nasal polyps (CRSwNP) and in a memory inflammatory mouse model. We find that toll-like receptor 4 (TLR4)+ILC2s, with similar markers to their human counterparts, expresse memory cell markers, persist over time, and respond more vigorously to a secondary unrelated antigen challenge in the mouse model. Genetic ablation of TLR4 or blockade by anti-TLR4 antibodies leads to the reduction of IL-13 expression from ILC2s and mucus production in mice. The assay for transposase-accessible chromatin sequencing further confirms the importance of accessible TLR4 gene loci and its down-stream signaling pathway in maintaining trained immunity of TLR4+ILC2s after repeated stimulation by HDM. Taken together, TLR4 has a function in trained immunity maintenance within ILC2s, which may contribute to disease chronicity through a non-specific immunological memory.https://doi.org/10.1038/s41467-025-62532-0 |
| spellingShingle | Yan Li Zaichuan Wang Su Duan Xue Wang Yuling Zhang Claus Bachert Nan Zhang Wei Wang Sun Ying Feng Lan Chengshuo Wang Luo Zhang TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases Nature Communications |
| title | TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| title_full | TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| title_fullStr | TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| title_full_unstemmed | TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| title_short | TLR4+group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| title_sort | tlr4 group 2 innate lymphoid cells contribute to persistent type 2 immunity in airway diseases |
| url | https://doi.org/10.1038/s41467-025-62532-0 |
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