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http://purl.uniprot.org/citations/36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/36853827http://www.w3.org/2000/01/rdf-schema#comment"Low capacity to produce ROS because of mutations in neutrophil cytosolic factor 1 (NCF1/p47phox), a component of NADPH oxidase 2 (NOX2) complex, is strongly associated with systemic lupus erythematosus in both humans and mouse models. Here, we aimed to identify the key immune cell type(s) and cellular mechanisms driving lupus pathogenesis under the condition of NCF1-dependent ROS deficiency. Using cell-specific Cre-deleter, human NCF1-339 variant knockin, and transgenic mouse strains, we show that low ROS production in plasmacytoid dendritic cells (pDCs) exacerbated both pristane-induced lupus and a potentially new Y-linked autoimmune accelerating locus-related spontaneous model by promoting pDC accumulation in multiple organs during lupus development, accompanied by elevated IFN-α levels and expression of IFN-stimulated genes. Mechanistic studies revealed that ROS deficiency enhanced pDC generation through the AKT/mTOR pathway and CCR2-mediated migration to tissues, which together with hyperactivation of the redox-sensitive stimulator of interferon genes/IFN-α/JAK1/STAT1 cascade further augmented type I IFN responses. More importantly, by suppressing these pathways, restoration of NOX2-derived ROS specifically in pDCs protected against lupus. These discoveries explain the causative effect of dysfunctional NCF1 in lupus and demonstrate the protective role of pDC-derived ROS in disease development driven by NCF1-dependent ROS deficiency."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.org/dc/terms/identifier"doi:10.1172/jci.insight.164875"xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Li Y."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Luo H."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Gaetani M."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Zubarev R.A."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Holmdahl R."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Urbonaviciute V."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Vegvari A."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Lyu H."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/author"Saei A.A."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/date"2023"xsd:gYear
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/name"JCI Insight"xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/pages"e164875"xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/title"NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions."xsd:string
http://purl.uniprot.org/citations/36853827http://purl.uniprot.org/core/volume"8"xsd:string
http://purl.uniprot.org/citations/36853827http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/36853827
http://purl.uniprot.org/citations/36853827http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/36853827
http://purl.uniprot.org/uniprot/#_F8WH69-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827
http://purl.uniprot.org/uniprot/#_Q09014-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827
http://purl.uniprot.org/uniprot/#_Q7TMH0-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827
http://purl.uniprot.org/uniprot/#_Q3UBI5-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827
http://purl.uniprot.org/uniprot/#_Q3U9Y3-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827
http://purl.uniprot.org/uniprot/#_Q3UA02-mappedCitation-36853827http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/36853827