Skin single cell universe identifies IL-1B/IL23A co-producing CD14+ type 3 dendritic cells in psoriasis

Inflammatory skin diseases including atopic dermatitis (AD) and psoriasis (PSO) are underpinned by dendritic cell- (DC) mediated T cell responses. Currently, the heterogeneous human cutaneous DC population is incompletely characterized, and its contribution to these diseases remains unclear. Here, we performed index-sorted single-cell flow cytometry and RNA-sequencing of lesional and non-lesional AD and PSO skin to identify macrophages and all DC subsets, including the newly-described mature LAMP3+BIRC3+ DC enriched in immunoregulatory molecules (mregDC) and DC3. By integrating our indexed data with published skin datasets, we generated a myeloid cell universe of DC and macrophage subsets in healthy and diseased skin. Importantly, we found that CD14+ DC3 were increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathologic in PSO. Our study comprehensively describes the molecular characteristics of macrophages and DC subsets in AD and PSO at single-cell resolution, and identifies CD14+ DC3 as potential promotors of inflammation in PSO. Overall design: We collected skin biopsies from two patients with AD and two with PSO, from both non-lesional and lesional areas, and prepared single cell suspensions by enzymatic digestion.