{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:38:48Z","timestamp":1790087928527,"version":"4.0.1"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T00:00:00Z","timestamp":1697414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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 <jats:italic>VSIG4<\/jats:italic> 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 <jats:italic>CCR2<\/jats:italic> 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 (<jats:italic>CCR7<\/jats:italic><jats:sup>high<\/jats:sup>, <jats:italic>TCF7<\/jats:italic><jats:sup>high<\/jats:sup>, and <jats:italic>HLA-DR<\/jats:italic><jats:sup>low<\/jats:sup>) and Treg2 (<jats:italic>CCR7<\/jats:italic><jats:sup>low<\/jats:sup>, <jats:italic>TCF7<\/jats:italic><jats:sup>low<\/jats:sup>, and <jats:italic>HLA-DR<\/jats:italic><jats:sup>high<\/jats:sup>). We found that the levels of Treg2 cells expressed significant levels of <jats:italic>CCR4<\/jats:italic> and <jats:italic>GATA3<\/jats:italic>, 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 <jats:italic>CCL2<\/jats:italic>, <jats:italic>PRSS23<\/jats:italic>, 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 <jats:italic>PTGDS<\/jats:italic> 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.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1231937","type":"journal-article","created":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T06:56:25Z","timestamp":1697439385000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Cell-type-specific molecular characterization of cells from circulation and kidney in IgA nephropathy with nephrotic 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