Human NCF190H Variant Promotes IL-23/IL-17—Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis

Li，Yanpeng1,2; Li，Zhilei3; Nandakumar，Kutty Selva2,4; Holmdahl，Rikard1,2

2023-07-01

10.3390/antiox12071348

Antioxidants   Impact Factor & Quartile

2076-3921

Recently, a major single nucleotide variant on the NCF1 gene, leading to an amino acid replacement from arginine to histidine at position 90 (NCF1), associated with low production of reactive 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 NCF1 variant promotes PsO and PsA (the MIP model). The NCF1-expressing mice had hyperactivated macrophages, expanded keratinocytes, and dramatically increased numbers of γδT17 cells with upregulated IL-17A, IL-23, and TNF-α. In addition, the JAK1/STAT3 signaling pathway was also upregulated in cells in the psoriatic skin tissues of Ncf1 mice. To summarize, a defined SNP (NCF1-339, also named NCF1) 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.

IL-23/IL-17 axis JAK-STAT macrophages NCF1 psoriasis ROS

SCI

English

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Knut och Alice Wallenbergs Stiftelse[2019-0059];Vetenskapsrådet[2019-01209];National Natural Science Foundation of China[32070913];Saint Mary’s University[C1034211];Sangmyung University[C1034211];Sapporo Medical University[C1034211];Shanghai Maritime University[C1034211];Singapore Management University[C1034211];Southern Medical University[C1034211];Southern Methodist University[C1034211];Sun Moon University[C1034211];Swansea Metropolitan University[C1034211];LEO Fondet[LF-OC-22-001023];

Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Food Science & Technology

Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Food Science & Technology

WOS:001037963800001

MDPI

2-s2.0-85165938097

Scopus

1.Division of Medical Inflammation Research,Department of Medical Biochemistry and Biophysics,Karolinska Institute,Stockholm,17177,Sweden
2.SMU-KI United Medical Inflammation Center,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,510515,China
3.Clinical Pharmacy Division of Pharmacy Department,Southern University of Science and Technology Hospital,Shenzhen,518055,China
4.Department of Environmental and Biosciences,School of Business,Innovation,and Sustainability,Halmstad University,Halmstad,30118,Sweden

Li，Yanpeng,Li，Zhilei,Nandakumar，Kutty Selva,等. Human NCF190H Variant Promotes IL-23/IL-17—Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis[J]. Antioxidants,2023,12(7).

Li，Yanpeng,Li，Zhilei,Nandakumar，Kutty Selva,&Holmdahl，Rikard.(2023).Human NCF190H Variant Promotes IL-23/IL-17—Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis.Antioxidants,12(7).

Li，Yanpeng,et al."Human NCF190H Variant Promotes IL-23/IL-17—Dependent Mannan-Induced Psoriasis and Psoriatic Arthritis".Antioxidants 12.7(2023).