Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome
Abstract Background Idiopathic nephrotic syndrome (INS) is a prevalent condition whose recurrence leads to multiple adverse effects. Previous studies on INS pathogenesis primarily focused on immune dysregulation, particularly T-cell changes and their correlation with cytokine shifts. Accumulating ev...
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BMC
2025-05-01
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| Online Access: | https://doi.org/10.1186/s40364-025-00790-2 |
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| author | Qiu-Yu Li Fei Liu Xiaoyi Li Minchao Kang Linnan Bai Tong Tong Chen Zheng Yanyan Jin Xiaojing Zhang Yi Xie Dandan Tian Yuanqing Pan Jingjing Wang Haidong Fu Na Jiao Junnan Wu JianHua Mao |
| author_facet | Qiu-Yu Li Fei Liu Xiaoyi Li Minchao Kang Linnan Bai Tong Tong Chen Zheng Yanyan Jin Xiaojing Zhang Yi Xie Dandan Tian Yuanqing Pan Jingjing Wang Haidong Fu Na Jiao Junnan Wu JianHua Mao |
| author_sort | Qiu-Yu Li |
| collection | DOAJ |
| description | Abstract Background Idiopathic nephrotic syndrome (INS) is a prevalent condition whose recurrence leads to multiple adverse effects. Previous studies on INS pathogenesis primarily focused on immune dysregulation, particularly T-cell changes and their correlation with cytokine shifts. Accumulating evidence suggests that B-cell dysfunction also plays a role. Nevertheless, a comprehensive understanding of the mechanisms and effective treatment strategies remains incomplete. Methods This study investigates changes in gene expressions and cellular interactions of immune cells at a single-cell level using peripheral blood mononuclear cells (PBMCs). And subsequently validated through quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Results We identified seven main clusters using unsupervised clustering of 103,213 high-quality single cells. Through unsupervised clustering, patient-specific T cells (IFI44L + CD4 + T cells) that exhibited a pronounced elevation of interferon-stimulated genes (ISGs) is identified. Activation of ISGs and interferon (IFN)-related pathways are also observed in other clusters. Specifically, this study demonstrates that interferon-γ (IFN-γ) plays a crucial role by promoting the interaction between B-cell activating factor (BAFF) and receptors on B cells. This interaction triggers the release of autoantibodies, thereby initiating INS pathogenesis. Furthermore, telitacicept has shown efficacy in treating pediatric patients with frequent relapse NS(FRNS). Conclusions Overall, our findings underscore the role of interferon and its related pathways in INS pathogenesis, providing novel therapeutic interventions for NS. |
| format | Article |
| id | doaj-art-12e517dc482a40e9983dcb586bbec3db |
| institution | OA Journals |
| issn | 2050-7771 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Biomarker Research |
| spelling | doaj-art-12e517dc482a40e9983dcb586bbec3db2025-08-20T01:53:25ZengBMCBiomarker Research2050-77712025-05-0113112010.1186/s40364-025-00790-2Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndromeQiu-Yu Li0Fei Liu1Xiaoyi Li2Minchao Kang3Linnan Bai4Tong Tong5Chen Zheng6Yanyan Jin7Xiaojing Zhang8Yi Xie9Dandan Tian10Yuanqing Pan11Jingjing Wang12Haidong Fu13Na Jiao14Junnan Wu15JianHua Mao16Department of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw HospitalDepartment of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw HospitalZhejiang University School of Medicine, Zhejiang UniversityZhejiang University School of Medicine, Zhejiang UniversityDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Clinical Laboratory, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, Quanzhou Women’s and Children’s HospitalDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthState Key Laboratory of Genetic Engineering, Fudan Microbiome Center, School of Life Sciences, Fudan UniversityDepartment of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw HospitalDepartment of Nephrology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthAbstract Background Idiopathic nephrotic syndrome (INS) is a prevalent condition whose recurrence leads to multiple adverse effects. Previous studies on INS pathogenesis primarily focused on immune dysregulation, particularly T-cell changes and their correlation with cytokine shifts. Accumulating evidence suggests that B-cell dysfunction also plays a role. Nevertheless, a comprehensive understanding of the mechanisms and effective treatment strategies remains incomplete. Methods This study investigates changes in gene expressions and cellular interactions of immune cells at a single-cell level using peripheral blood mononuclear cells (PBMCs). And subsequently validated through quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), and flow cytometry. Results We identified seven main clusters using unsupervised clustering of 103,213 high-quality single cells. Through unsupervised clustering, patient-specific T cells (IFI44L + CD4 + T cells) that exhibited a pronounced elevation of interferon-stimulated genes (ISGs) is identified. Activation of ISGs and interferon (IFN)-related pathways are also observed in other clusters. Specifically, this study demonstrates that interferon-γ (IFN-γ) plays a crucial role by promoting the interaction between B-cell activating factor (BAFF) and receptors on B cells. This interaction triggers the release of autoantibodies, thereby initiating INS pathogenesis. Furthermore, telitacicept has shown efficacy in treating pediatric patients with frequent relapse NS(FRNS). Conclusions Overall, our findings underscore the role of interferon and its related pathways in INS pathogenesis, providing novel therapeutic interventions for NS.https://doi.org/10.1186/s40364-025-00790-2Idiopathic nephrotic syndromescRNA-seqIFNPBMCs |
| spellingShingle | Qiu-Yu Li Fei Liu Xiaoyi Li Minchao Kang Linnan Bai Tong Tong Chen Zheng Yanyan Jin Xiaojing Zhang Yi Xie Dandan Tian Yuanqing Pan Jingjing Wang Haidong Fu Na Jiao Junnan Wu JianHua Mao Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome Biomarker Research Idiopathic nephrotic syndrome scRNA-seq IFN PBMCs |
| title | Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome |
| title_full | Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome |
| title_fullStr | Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome |
| title_full_unstemmed | Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome |
| title_short | Single cell analysis identified IFN signaling activation contributes to the pathogenesis of pediatric steroid-sensitive nephrotic syndrome |
| title_sort | single cell analysis identified ifn signaling activation contributes to the pathogenesis of pediatric steroid sensitive nephrotic syndrome |
| topic | Idiopathic nephrotic syndrome scRNA-seq IFN PBMCs |
| url | https://doi.org/10.1186/s40364-025-00790-2 |
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