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Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis

Authors: Nakamizo, Satoshi; Dutertre, Charles-Antoine; Khalilnezhad, Ahad; Zhang, Xiao Meng; Lim, Shawn; Lum, Josephine; Koh, Geraldine; Foong, Charlene; Yong, Pearly Jean Ai; Tan, Kahbing Jasmine; Sato, Reiko; Tomari, Kaori; Yvan-Charvet, Laurent; He, Helen; Guttman-Yassky, Emma; Malleret, Benoit; Shibuya, Rintaro; Iwata, Masashi; Janela, Baptiste; Goto, Tsuyoshi; Lucinda, Tan Siyun; Tang, Mark B.Y.; Theng, Colin; Julia, Valerie; Hacini-Rachinel, Feriel; Kabashima, Kenji; Ginhoux, Florent

Online: https://doi.org/10.1084/jem.20202345

Issue: J Exp Med. 2021 Sep 6;218(9):e20202345.


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.