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 Foong, Pearly Jean Ai Yong, Kahbing Jasmine Tan, Reiko Sato, Kaori Tomari, Laurent Yvan-Charvet, Helen He, Emma Guttman-Yassky, Benoit Malleret, Rintaro Shibuya, Masashi Iwata, Baptiste Janela, Tsuyoshi GotoTan Siyun Lucinda, Mark B.Y. Tang, Colin Theng, Valerie Julia, Feriel Hacini-Rachinel, Kenji Kabashima, Florent Ginhoux

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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.

Original languageEnglish
Article numbere20202345
JournalJournal of Experimental Medicine
Volume218
Issue number9
DOIs
StatePublished - 19 Jul 2021

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