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<p>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 <i>IL4I1</i><sup>+</sup><i>CD200</i><sup>+</sup><i>CCR7</i><sup>+</sup> dendritic cells (CCR7<sup>+</sup> 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<sup>+</sup> DC completely abrogates IL-23 production in a mouse model of psoriasis, while enforced expression of IL-23a in CCR7<sup>+</sup> DC elicits not only αβT cell-driven psoriasis-like skin disease, but also arthritis. CCR7<sup>+</sup> DC co-localize with CD161<sup>+</sup> IL-17-producing T cells and KRT17<sup>+</sup> keratinocytes, which are located in the outermost layers of psoriatic epidermis and exhibit IL-17 downstream signatures. Our data thus identify CCR7<sup>+</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月15日

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  • 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,
  • Honglin Wang

摘要

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.