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CCR7+ dendritic cells expressing both IL-23A and IL-12B potentially contribute to psoriasis relapse

Yang Sun, Fangzhou Lou, Xiaojie Cai, Zhikai Wang, Xiuli Yang, Libo Sun, Zhenyao Xu, Siyu Deng, Zhouwei Wu, Zhaoyuan Liu, Yu-Ling Shi, Florent Ginhoux and Honglin Wang ()
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Yang Sun: Shanghai Jiao Tong University School of Medicine
Fangzhou Lou: Shanghai Jiao Tong University School of Medicine
Xiaojie Cai: Shanghai Jiao Tong University School of Medicine
Zhikai Wang: Shanghai Jiao Tong University School of Medicine
Xiuli Yang: Shanghai Jiao Tong University School of Medicine
Libo Sun: Shanghai Jiao Tong University School of Medicine
Zhenyao Xu: Shanghai Jiao Tong University School of Medicine
Siyu Deng: Shanghai Jiao Tong University School of Medicine
Zhouwei Wu: Shanghai Jiao Tong University School of Medicine
Zhaoyuan Liu: Shanghai Jiao Tong University School of Medicine
Yu-Ling Shi: Tongji University School of Medicine
Florent Ginhoux: Shanghai Jiao Tong University School of Medicine
Honglin Wang: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract Interleukin (IL)−23 is the master pathogenic cytokine in psoriasis and neutralization of IL-23 alleviates psoriasis. Psoriasis relapses after the withdrawal of anti-IL-23 antibodies, and the persistence of IL-23-producing cells potentially contributes to such recurrence, but the cellular source of IL-23 is unclear. Here we show that IL4I1+CD200+CCR7+ dendritic cells (CCR7+ DC) are the main producer of IL-23 by concomitantly expressing the IL-23A and IL-12B subunits in human psoriatic skin. Deletion of CCR7+ DC completely abrogates IL-23 production in a mouse model of psoriasis, while enforced expression of IL-23a in CCR7+ DC elicits not only αβT cell-driven psoriasis-like skin disease, but also arthritis. CCR7+ DC co-localize with CD161+ IL-17-producing T cells and KRT17+ keratinocytes, which are located in the outermost layers of psoriatic epidermis and exhibit IL-17 downstream signatures. Our data thus identify CCR7+ DC as the source of IL-23 in psoriasis, and paves the way for IL-23-targeting therapy for suppressing the relapse of chronic inflammatory disorders like psoriasis.

Date: 2025
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DOI: 10.1038/s41467-025-62874-9

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