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oxygen species (ROS), was found to be causative for several autoimmune diseases. Psoriasis in the skin (PsO) and psoriatic arthritis (PsA) were induced with mannan by intraperitoneal injection or epicutaneous application, evaluated by visual and histology scoring. Immunostaining was used to identify macrophages, NCF1, and keratinocytes. The population of immune cells was quantified by flow cytometry, gene expression was analyzed by RT-qPCR, and the JAK\/STAT signaling pathway was investigated by immunohistochemical staining and western blot. We found that the low ROS responder NCF190H variant promotes PsO and PsA (the MIP model). The NCF190H-expressing mice had hyperactivated macrophages, expanded keratinocytes, and dramatically increased numbers of \u03b3\u03b4T17 cells with upregulated IL-17A, IL-23, and TNF-\u03b1. In addition, the JAK1\/STAT3 signaling pathway was also upregulated in cells in the psoriatic skin tissues of Ncf190H mice. To summarize, a defined SNP (NCF1-339, also named NCF190H) was found to activate the IL-23\/IL-17 axis and JAK-STAT signaling pathways, leading to hyperactivation of macrophages and keratinocytes and causing mouse psoriasis and psoriatic arthritis.<\/jats:p>","DOI":"10.3390\/antiox12071348","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:25:21Z","timestamp":1687911921000},"page":"1348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Human NCF190H Variant Promotes IL-23\/IL-17\u2013Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-4390","authenticated-orcid":false,"given":"Yanpeng","family":"Li","sequence":"first","affiliation":[{"name":"Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"SMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3439-0986","authenticated-orcid":false,"given":"Zhilei","family":"Li","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy Division of Pharmacy Department, Southern University of Science and Technology Hospital, Shenzhen 518055, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7790-8197","authenticated-orcid":false,"given":"Kutty Selva","family":"Nandakumar","sequence":"additional","affiliation":[{"name":"SMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"},{"name":"Department of Environmental and Biosciences, School of Business, Innovation, and Sustainability, Halmstad University, 30118 Halmstad, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4969-2576","authenticated-orcid":false,"given":"Rikard","family":"Holmdahl","sequence":"additional","affiliation":[{"name":"Division of Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 17177 Stockholm, Sweden"},{"name":"SMU-KI United Medical Inflammation Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1001\/jama.2020.4006","article-title":"Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review","volume":"323","author":"Armstrong","year":"2020","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/ng1058","article-title":"Positional identification of Ncf1 as a gene that regulates arthritis severity in rats","volume":"33","author":"Olofsson","year":"2003","journal-title":"Nat. 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