Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets
Background Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the axial joints. Immune cells play a key role in the pathogenesis of AS. This study integrated bioinformatics methods with experimental validation to explore the role of natural killer (NK) cells in AS.Met...
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Taylor & Francis Group
2025-12-01
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| Series: | Annals of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/07853890.2025.2457523 |
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| author | Yuling Chen Yan Li Yuan Xu Qing Lv Yuanchun Ye Jieruo Gu |
| author_facet | Yuling Chen Yan Li Yuan Xu Qing Lv Yuanchun Ye Jieruo Gu |
| author_sort | Yuling Chen |
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| description | Background Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the axial joints. Immune cells play a key role in the pathogenesis of AS. This study integrated bioinformatics methods with experimental validation to explore the role of natural killer (NK) cells in AS.Methods Two microarray datasets, GSE25101 and GSE73754, were selected, and the scRNA-seq data were obtained from GSE194315 and Liu’s research. Differentially expressed genes (DEGs) and functional enrichment analysis were performed respectively. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules of co-expressed genes and genes involved in NK cell function. The diagnostic value of the identified key genes was evaluated using ROC curves, logistic regression analysis, and a nomogram. Real-time PCR (RT-PCR) was used to quantified the expression of genes. Statistical analysis was conducted using the R software package, and a p-value of less than 0.05 was considered statistically significant.Results Pathways enrichment analysis revealed the involvement of NK cell-mediated immune pathways and regulation of the innate immune response, indicating the crucial role of innate immunity, especially NK cells, in AS pathogenesis. The construction of a co-expression network revealed that the MElightyellow module was most relevant to the NK cell-mediated immune pathway. IL2RB, CD247, PLEKHF1, EOMES, S1PR5, FGFBP2 from the MElightyellow module were identified as key genes involved in NK cell-mediated immune response and served as potential diagnostic biomarkers for AS, with moderate to high diagnostic values based on AUC values. Further analysis using scRNA-seq profiling revealed the higher expression level of IL2RB, CD247, PLEKHF1, S1PR5, FGFBP2 in NK cells compared to that in other cell types. CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 were reduced expressed in AS patients as compare to control group verified by scRNA-seq data, CD247, EOMES, FGFBP2, IL2RB and S1PR5 were reduced expressed verified by RT-PCR, and PLEKHF1, S1PR5, and FGFBP2 was upregulated after TNF-α blocker therapy.Conclusion The study revealed the potential role of NK cells and identified IL2RB, CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 as key genes associated with NK cells in the pathogenesis of AS. |
| format | Article |
| id | doaj-art-114f3f9e69a74f589db1797ba7d5e202 |
| institution | Kabale University |
| issn | 0785-3890 1365-2060 |
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| publishDate | 2025-12-01 |
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| spelling | doaj-art-114f3f9e69a74f589db1797ba7d5e2022025-01-24T14:36:19ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2457523Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targetsYuling Chen0Yan Li1Yuan Xu2Qing Lv3Yuanchun Ye4Jieruo Gu5Department of Rheumatology and Immunology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of ChinaDepartment of Scientific Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of ChinaDepartment of Clinical Laboratory, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of ChinaDepartment of Rheumatology and Immunology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of ChinaSchool of Science, Shenzhen Campus of Sun Yat-sen University, Shenzhen, People’s Republic of ChinaDepartment of Rheumatology and Immunology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, People’s Republic of ChinaBackground Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the axial joints. Immune cells play a key role in the pathogenesis of AS. This study integrated bioinformatics methods with experimental validation to explore the role of natural killer (NK) cells in AS.Methods Two microarray datasets, GSE25101 and GSE73754, were selected, and the scRNA-seq data were obtained from GSE194315 and Liu’s research. Differentially expressed genes (DEGs) and functional enrichment analysis were performed respectively. Weighted gene co-expression network analysis (WGCNA) was conducted to identify key modules of co-expressed genes and genes involved in NK cell function. The diagnostic value of the identified key genes was evaluated using ROC curves, logistic regression analysis, and a nomogram. Real-time PCR (RT-PCR) was used to quantified the expression of genes. Statistical analysis was conducted using the R software package, and a p-value of less than 0.05 was considered statistically significant.Results Pathways enrichment analysis revealed the involvement of NK cell-mediated immune pathways and regulation of the innate immune response, indicating the crucial role of innate immunity, especially NK cells, in AS pathogenesis. The construction of a co-expression network revealed that the MElightyellow module was most relevant to the NK cell-mediated immune pathway. IL2RB, CD247, PLEKHF1, EOMES, S1PR5, FGFBP2 from the MElightyellow module were identified as key genes involved in NK cell-mediated immune response and served as potential diagnostic biomarkers for AS, with moderate to high diagnostic values based on AUC values. Further analysis using scRNA-seq profiling revealed the higher expression level of IL2RB, CD247, PLEKHF1, S1PR5, FGFBP2 in NK cells compared to that in other cell types. CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 were reduced expressed in AS patients as compare to control group verified by scRNA-seq data, CD247, EOMES, FGFBP2, IL2RB and S1PR5 were reduced expressed verified by RT-PCR, and PLEKHF1, S1PR5, and FGFBP2 was upregulated after TNF-α blocker therapy.Conclusion The study revealed the potential role of NK cells and identified IL2RB, CD247, PLEKHF1, EOMES, S1PR5, and FGFBP2 as key genes associated with NK cells in the pathogenesis of AS.https://www.tandfonline.com/doi/10.1080/07853890.2025.2457523Ankylosing spondylitisnatural killer cellsdiagnostic biomarkerssingle-cell RNA sequencing |
| spellingShingle | Yuling Chen Yan Li Yuan Xu Qing Lv Yuanchun Ye Jieruo Gu Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets Annals of Medicine Ankylosing spondylitis natural killer cells diagnostic biomarkers single-cell RNA sequencing |
| title | Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets |
| title_full | Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets |
| title_fullStr | Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets |
| title_full_unstemmed | Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets |
| title_short | Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets |
| title_sort | revealing the role of natural killer cells in ankylosing spondylitis identifying diagnostic biomarkers and therapeutic targets |
| topic | Ankylosing spondylitis natural killer cells diagnostic biomarkers single-cell RNA sequencing |
| url | https://www.tandfonline.com/doi/10.1080/07853890.2025.2457523 |
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