Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps
Abstract Sophisticated interactions between stromal and immune cells play crucial roles in various biological and pathological processes. In chronic rhinosinusitis with nasal polyps (CRSwNP), the upper airway inflammation in many patients is driven by TH2, ILC2, and eosinophils, thus being treated w...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54685-1 |
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| author | Cui-Lian Guo Chong-Shu Wang Zhi-Chao Wang Fei-Fan Liu Lin Liu Yang Yang Xia Li Bei Guo Ruo-Yu Lu Bo Liao Jin-Xin Liu Hai Wang Jia Song Yin Yao Li-Ping Zhu Di Yu Zheng Liu |
| author_facet | Cui-Lian Guo Chong-Shu Wang Zhi-Chao Wang Fei-Fan Liu Lin Liu Yang Yang Xia Li Bei Guo Ruo-Yu Lu Bo Liao Jin-Xin Liu Hai Wang Jia Song Yin Yao Li-Ping Zhu Di Yu Zheng Liu |
| author_sort | Cui-Lian Guo |
| collection | DOAJ |
| description | Abstract Sophisticated interactions between stromal and immune cells play crucial roles in various biological and pathological processes. In chronic rhinosinusitis with nasal polyps (CRSwNP), the upper airway inflammation in many patients is driven by TH2, ILC2, and eosinophils, thus being treated with glucocorticoids and anti-type 2 inflammation biologics. The resistance to these therapies is often associated with neutrophilic inflammation, which has also been widely identified in CRSwNP, but the underlying mechanisms remain unclear. Using single-cell analysis, spatial transcriptomics, and T-cell receptor sequencing, we identify an increased presence of granzyme K+(GZMK+) CD8+ T cells in NPs, which possess a phenotype distinct from the cytotoxic GZMB+ effector CD8+ T subset. GZMK+CD8+ T cells are found to express CXCR4 and interact with CXCL12-secreting fibroblasts, inducing the latter to produce neutrophil chemoattractants in a manner uniquely mediated by GZMK but not other granzymes. This GZMK+CD8+ T cell-fibroblast crosstalk is also observed in other inflammatory diseases. Furthermore, GZMK+CD8+ T cells exhibit a selective expansion of clones that recognize Epstein-Barr virus. Here, we show that GZMK marks a phenotypically distinct subset of effector CD8+ T cells that promote neutrophilic inflammation. |
| format | Article |
| id | doaj-art-b7c6cb64bdd343beab624f5f7c36a4ad |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-b7c6cb64bdd343beab624f5f7c36a4ad2024-12-01T12:33:16ZengNature PortfolioNature Communications2041-17232024-11-0115112210.1038/s41467-024-54685-1Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polypsCui-Lian Guo0Chong-Shu Wang1Zhi-Chao Wang2Fei-Fan Liu3Lin Liu4Yang Yang5Xia Li6Bei Guo7Ruo-Yu Lu8Bo Liao9Jin-Xin Liu10Hai Wang11Jia Song12Yin Yao13Li-Ping Zhu14Di Yu15Zheng Liu16Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan BiobankFrazer Institute, Faculty of Medicine, University of QueenslandWuhan BiobankDepartment of Otolaryngology-Head and Neck Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and TechnologyFrazer Institute, Faculty of Medicine, University of QueenslandDepartment of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Sophisticated interactions between stromal and immune cells play crucial roles in various biological and pathological processes. In chronic rhinosinusitis with nasal polyps (CRSwNP), the upper airway inflammation in many patients is driven by TH2, ILC2, and eosinophils, thus being treated with glucocorticoids and anti-type 2 inflammation biologics. The resistance to these therapies is often associated with neutrophilic inflammation, which has also been widely identified in CRSwNP, but the underlying mechanisms remain unclear. Using single-cell analysis, spatial transcriptomics, and T-cell receptor sequencing, we identify an increased presence of granzyme K+(GZMK+) CD8+ T cells in NPs, which possess a phenotype distinct from the cytotoxic GZMB+ effector CD8+ T subset. GZMK+CD8+ T cells are found to express CXCR4 and interact with CXCL12-secreting fibroblasts, inducing the latter to produce neutrophil chemoattractants in a manner uniquely mediated by GZMK but not other granzymes. This GZMK+CD8+ T cell-fibroblast crosstalk is also observed in other inflammatory diseases. Furthermore, GZMK+CD8+ T cells exhibit a selective expansion of clones that recognize Epstein-Barr virus. Here, we show that GZMK marks a phenotypically distinct subset of effector CD8+ T cells that promote neutrophilic inflammation.https://doi.org/10.1038/s41467-024-54685-1 |
| spellingShingle | Cui-Lian Guo Chong-Shu Wang Zhi-Chao Wang Fei-Fan Liu Lin Liu Yang Yang Xia Li Bei Guo Ruo-Yu Lu Bo Liao Jin-Xin Liu Hai Wang Jia Song Yin Yao Li-Ping Zhu Di Yu Zheng Liu Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps Nature Communications |
| title | Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| title_full | Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| title_fullStr | Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| title_full_unstemmed | Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| title_short | Granzyme K+CD8+ T cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| title_sort | granzyme k cd8 t cells interact with fibroblasts to promote neutrophilic inflammation in nasal polyps |
| url | https://doi.org/10.1038/s41467-024-54685-1 |
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