{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:32:22Z","timestamp":1793035942198,"version":"4.5.0"},"reference-count":74,"publisher":"American Society for Clinical Investigation","issue":"7","license":[{"start":{"date-parts":[[2023,4,10]],"date-time":"2023-04-10T00:00:00Z","timestamp":1681084800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swedish Science Research Council","award":["2019-01209"],"award-info":[{"award-number":["2019-01209"]}]},{"name":"KA Wallenberg Foundation","award":["KAW 2019.0059"],"award-info":[{"award-number":["KAW 2019.0059"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,4,10]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>NCF1<\/jats:italic>\n                    -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\u2013related spontaneous model by promoting pDC accumulation in multiple organs during lupus development, accompanied by elevated IFN-\u03b1 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-\u03b1\/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.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.164875","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T12:00:24Z","timestamp":1677585624000},"source":"Crossref","is-referenced-by-count":41,"title":["NCF1-dependent production of ROS protects against lupus by regulating plasmacytoid dendritic cell development and functions"],"prefix":"10.1172","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4249-0138","authenticated-orcid":true,"given":"Huqiao","family":"Luo","sequence":"first","affiliation":[{"name":"Division of Medical Inflammation Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilma","family":"Urbonaviciute","sequence":"additional","affiliation":[{"name":"Division of Medical Inflammation 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