Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis
Satoshi Nakamizo, Charles‐Antoine Dutertre, Ahad Khalilnezhad, Xiao Meng Zhang, Shawn Lim, Josephine Lum, Geraldine Koh, Charlene S.F. Foong, Pearly Yong, Kahbing Jasmine Tan, Reiko Sato, Kaori Tomari, Laurent Yvan‐Charvet, Helen He, Emma Guttman‐Yassky, Benoît Malleret, Rintaro Shibuya, Masashi Iwata, Baptiste Janela, Tsuyoshi Goto, Tan Siyun Lucinda, Mark Boon Yang Tang, Colin Theng, Valérie Julia, Fériel Hacini‐Rachinel, Kenji Kabashima, Florent Ginhoux
Abstract
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 nonlesional AD and PSO skin to identify macrophages and all DC subsets, including the newly described mature LAMP3+BIRC3+ DCs enriched in immunoregulatory molecules (mregDC) and CD14+ 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+ DC3s increased in PSO lesional skin and co-produced IL1B and IL23A, which are pathological 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+ DC3s as potential promoters of inflammation in PSO.