Interleukin (IL)-23 is the master pathogenic cytokine in psoriasis and neutralization of IL-23 alleviates psoriasis. Psoriasis relapses after the withdrawal of IL-23 antibodies, and the persistence of IL-23-producing cells probably contributes to such recurrence. However, the cellular source of IL-23 was unclear, which hinders the development of targeted therapies focusing on modulating IL-23 expression aimed at resolving relapse. Here, we showed that IL4I1 + CD200 + CCR7 + dendritic cells (CCR7 + DC) dominantly produced IL-23 by concomitantly expressing the IL-23A and IL-12B subunits in human psoriatic skin. Deletion of CCR7 + DC completely abrogated IL-23 production in a mouse model of psoriasis and enforced expression of IL-23a in CCR7 + DC elicited not only αβT cell-driven psoriasis-like skin disease, but also arthritis. CCR7 + DC co-localized with CD161 + IL-17-producing T cells and KRT17 + keratinocytes, which were located in the outermost layers of psoriatic epidermis and strongly exhibited IL-17 downstream signatures. Based on these data, we identified CCR7 + DC as the source of IL-23 in psoriasis, which paves the way for the design of therapies focused on manipulating IL-23 production that may resolve the relapse of chronic inflammatory disorders like psoriasis.

CCR7+Dendritic Cells Define a Type 17 Module in Psoriasis