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

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.