Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome
Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cel...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-10-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231937/full |
| _version_ | 1797659542027239424 |
|---|---|
| author | Qilin Chen Qilin Chen Qilin Chen Huimin Jiang Huimin Jiang Huimin Jiang Rong Ding Jinjie Zhong Jinjie Zhong Jinjie Zhong Longfei Li Junli Wan Junli Wan Xiaoqian Feng Xiaoqian Feng Xiaoqian Feng Liping Peng Liping Peng Liping Peng Xia Yang Xia Yang Xia Yang Han Chen Han Chen Anshuo Wang Anshuo Wang Jia Jiao Jia Jiao Qin Yang Qin Yang Xuelan Chen Xuelan Chen Xiaoqin Li Xiaoqin Li Lin Shi Lin Shi Gaofu Zhang Gaofu Zhang Mo Wang Mo Wang Haiping Yang Haiping Yang Qiu Li Qiu Li Qiu Li |
| author_facet | Qilin Chen Qilin Chen Qilin Chen Huimin Jiang Huimin Jiang Huimin Jiang Rong Ding Jinjie Zhong Jinjie Zhong Jinjie Zhong Longfei Li Junli Wan Junli Wan Xiaoqian Feng Xiaoqian Feng Xiaoqian Feng Liping Peng Liping Peng Liping Peng Xia Yang Xia Yang Xia Yang Han Chen Han Chen Anshuo Wang Anshuo Wang Jia Jiao Jia Jiao Qin Yang Qin Yang Xuelan Chen Xuelan Chen Xiaoqin Li Xiaoqin Li Lin Shi Lin Shi Gaofu Zhang Gaofu Zhang Mo Wang Mo Wang Haiping Yang Haiping Yang Qiu Li Qiu Li Qiu Li |
| author_sort | Qilin Chen |
| collection | DOAJ |
| description | Nephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7high, TCF7high, and HLA-DRlow) and Treg2 (CCR7low, TCF7low, and HLA-DRhigh). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future. |
| first_indexed | 2024-03-11T18:16:36Z |
| format | Article |
| id | doaj.art-d5503b70c6594198a04226abbd6a8428 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T18:16:36Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-d5503b70c6594198a04226abbd6a84282023-10-16T06:55:59ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12319371231937Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndromeQilin Chen0Qilin Chen1Qilin Chen2Huimin Jiang3Huimin Jiang4Huimin Jiang5Rong Ding6Jinjie Zhong7Jinjie Zhong8Jinjie Zhong9Longfei Li10Junli Wan11Junli Wan12Xiaoqian Feng13Xiaoqian Feng14Xiaoqian Feng15Liping Peng16Liping Peng17Liping Peng18Xia Yang19Xia Yang20Xia Yang21Han Chen22Han Chen23Anshuo Wang24Anshuo Wang25Jia Jiao26Jia Jiao27Qin Yang28Qin Yang29Xuelan Chen30Xuelan Chen31Xiaoqin Li32Xiaoqin Li33Lin Shi34Lin Shi35Gaofu Zhang36Gaofu Zhang37Mo Wang38Mo Wang39Haiping Yang40Haiping Yang41Qiu Li42Qiu Li43Qiu Li44Department of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaNanjing Jiangbei New Area Biopharmaceutical Public Service Platform Co. Ltd, Nanjing, Jiangsu, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaNanjing Jiangbei New Area Biopharmaceutical Public Service Platform Co. Ltd, Nanjing, Jiangsu, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaDepartment of Nephrology, Children’s Hospital of Chongqing Medical University, Chongqing, ChinaNational Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, ChinaChongqing Key Laboratory of Pediatrics, Chongqing, ChinaNephrotic syndrome (NS) is a relatively rare and serious presentation of IgA nephropathy (IgAN) (NS-IgAN). Previous research has suggested that the pathogenesis of NS-IgAN may involve circulating immune imbalance and kidney injury; however, this has yet to be fully elucidated. To investigate the cellular and molecular status of NS-IgAN, we performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) and kidney cells from pediatric patients diagnosed with NS-IgAN by renal biopsy. Consistently, the proportion of intermediate monocytes (IMs) in NS-IgAN patients was higher than in healthy controls. Furthermore, flow cytometry confirmed that IMs were significantly increased in pediatric patients with NS. The characteristic expression of VSIG4 and MHC class II molecules and an increase in oxidative phosphorylation may be important features of IMs in NS-IgAN. Notably, we found that the expression level of CCR2 was significantly increased in the CMs, IMs, and NCMs of patients with NS-IgAN. This may be related to kidney injury. Regulatory T cells (Tregs) are classified into two subsets of cells: Treg1 (CCR7high, TCF7high, and HLA-DRlow) and Treg2 (CCR7low, TCF7low, and HLA-DRhigh). We found that the levels of Treg2 cells expressed significant levels of CCR4 and GATA3, which may be related to the recovery of kidney injury. The state of NS in patients was closely related to podocyte injury. The expression levels of CCL2, PRSS23, and genes related to epithelial-mesenchymal transition were significantly increased in podocytes from NS-IgAN patients. These represent key features of podocyte injury. Our analysis suggests that PTGDS is significantly downregulated following injury and may represent a new marker for podocytes. In this study, we systematically analyzed molecular events in the circulatory system and kidney tissue of pediatric patients with NS-IgAN, which provides new insights for targeted therapy in the future.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231937/fullIgA nephropathynephrotic syndromesingle-cell RNA sequencingperipheral blood mononuclear cellspodocyte |
| spellingShingle | Qilin Chen Qilin Chen Qilin Chen Huimin Jiang Huimin Jiang Huimin Jiang Rong Ding Jinjie Zhong Jinjie Zhong Jinjie Zhong Longfei Li Junli Wan Junli Wan Xiaoqian Feng Xiaoqian Feng Xiaoqian Feng Liping Peng Liping Peng Liping Peng Xia Yang Xia Yang Xia Yang Han Chen Han Chen Anshuo Wang Anshuo Wang Jia Jiao Jia Jiao Qin Yang Qin Yang Xuelan Chen Xuelan Chen Xiaoqin Li Xiaoqin Li Lin Shi Lin Shi Gaofu Zhang Gaofu Zhang Mo Wang Mo Wang Haiping Yang Haiping Yang Qiu Li Qiu Li Qiu Li Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome Frontiers in Immunology IgA nephropathy nephrotic syndrome single-cell RNA sequencing peripheral blood mononuclear cells podocyte |
| title | Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome |
| title_full | Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome |
| title_fullStr | Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome |
| title_full_unstemmed | Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome |
| title_short | Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome |
| title_sort | cell type specific molecular characterization of cells from circulation and kidney in iga nephropathy with nephrotic syndrome |
| topic | IgA nephropathy nephrotic syndrome single-cell RNA sequencing peripheral blood mononuclear cells podocyte |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231937/full |
| work_keys_str_mv | AT qilinchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qilinchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qilinchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT huiminjiang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT huiminjiang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT huiminjiang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT rongding celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT jinjiezhong celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT jinjiezhong celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT jinjiezhong celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT longfeili celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT junliwan celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT junliwan celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiaoqianfeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiaoqianfeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiaoqianfeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT lipingpeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT lipingpeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT lipingpeng celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiayang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiayang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiayang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT hanchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT hanchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT anshuowang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT anshuowang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT jiajiao celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT jiajiao celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qinyang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qinyang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xuelanchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xuelanchen celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiaoqinli celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT xiaoqinli celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT linshi celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT linshi celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT gaofuzhang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT gaofuzhang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT mowang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT mowang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT haipingyang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT haipingyang celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qiuli celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qiuli celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome AT qiuli celltypespecificmolecularcharacterizationofcellsfromcirculationandkidneyiniganephropathywithnephroticsyndrome |