Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic syndrome

作者全名："Chen, Qilin; Jiang, Huimin; Ding, Rong; Zhong, Jinjie; Li, Longfei; Wan, Junli; Feng, Xiaoqian; Peng, Liping; Yang, Xia; Chen, Han; Wang, Anshuo; Jiao, Jia; Yang, Qin; Chen, Xuelan; Li, Xiaoqin; Shi, Lin; Zhang, Gaofu; Wang, Mo; Yang, Haiping; Li, Qiu"

作者地址："[Chen, Qilin; Jiang, Huimin; Zhong, Jinjie; Wan, Junli; Feng, Xiaoqian; Peng, Liping; Yang, Xia; Chen, Han; Wang, Anshuo; Jiao, Jia; Yang, Qin; Chen, Xuelan; Li, Xiaoqin; Shi, Lin; Zhang, Gaofu; Wang, Mo; Yang, Haiping; Li, Qiu] Chongqing Med Univ, Childrens Hosp, Dept Nephrol, Chongqing, Peoples R China; [Chen, Qilin; Jiang, Huimin; Zhong, Jinjie; Wan, Junli; Feng, Xiaoqian; Peng, Liping; Yang, Xia; Chen, Han; Wang, Anshuo; Jiao, Jia; Yang, Qin; Chen, Xuelan; Li, Xiaoqin; Shi, Lin; Zhang, Gaofu; Wang, Mo; Yang, Haiping; Li, Qiu] Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing, Peoples R China; [Chen, Qilin; Jiang, Huimin; Zhong, Jinjie; Feng, Xiaoqian; Peng, Liping; Yang, Xia; Li, Qiu] Chongqing Key Lab Pediat, Chongqing, Peoples R China; [Ding, Rong; Li, Longfei] Nanjing Jiangbei New Area Biopharmaceut Publ Serv, Nanjing, Jiangsu, Peoples R China"

通信作者："Yang, HP; Li, Q (通讯作者)，Chongqing Med Univ, Childrens Hosp, Dept Nephrol, Chongqing, Peoples R China.; Yang, HP; Li, Q (通讯作者)，Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ Key Lab Child Dev & Disorders, Chongqing, Peoples R China.; Li, Q (通讯作者)，Chongqing Key Lab Pediat, Chongqing, Peoples R China."

来源：FRONTIERS IN IMMUNOLOGY

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001089104100001

JCR分区：Q1

影响因子：5.7

年份：2023

卷号：14

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：IgA nephropathy; nephrotic syndrome; single-cell RNA sequencing; peripheral blood mononuclear cells; podocyte

摘要："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 (CCR7(high), TCF7(high), and HLA-DRlow) and Treg2 (CCR7(low), TCF7(low), 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."

基金机构："This work was supported by the National Key Ramp;D Program of China (Grant No. 2022YFC2705101), the Chongqing Science and Health Joint Medical Research Project (Grant No. 2023GGXM001), the Program for Youth Innovation in Future Medicine, Chongqing Medical [2022YFC2705101]; National Key Ramp;D Program of China [2023GGXM001]; Chongqing Science and Health Joint Medical Research Project [W0098]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [2011010006602511]; Special Fund For Postdoctoral Research Projects of Chongqing, China"

基金资助正文："We thank all the participants and their guardians for this study.r This work was supported by the National Key R&D Program of China (Grant No. 2022YFC2705101), the Chongqing Science and Health Joint Medical Research Project (Grant No. 2023GGXM001), the Program for Youth Innovation in Future Medicine, Chongqing Medical University (Grant No. W0098), and through the Special Fund For Postdoctoral Research Projects of Chongqing, China (Grant No. 2011010006602511)."