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, Yuling Shi, Florent Ginhoux, Honglin Wang
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. Chronic inflammation like psoriasis can be treated with anti-IL-23 antibodies, but relapses often occur after treatment cessation. Here the authors show that CCR7+ dendritic cells (DC) persist in human psoriasis skin, while depletion of CCR7+ DC abrogates psoriasis in mouse models, thereby hinting a function of IL-23 derived from CCR7+ DC in chronic inflammation.