Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A 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 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.
Competing Interests: Disclosures:   E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Almirall, Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boerhinger-Ingelhiem, Celgene, Dermavant, DS Biopharma, Eli Lilly, Galderma,Glenmark/Ichnos Sciences, Innovaderm, Janssen, Kiniksa, Kyowa Kirin, Leo Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron Pharmaceuticals, Inc., Sienna Biopharma, UCB, and Union Therapeutics/Antibiotx; and is a consultant for Abbvie, Aditum Bio, Almirall, Alpine, Amgen, Arena, Asana Biosciences, AstraZeneca, Bluefin Biomedicine, Boerhinger-Ingelhiem, Boston Pharmaceuticals, Botanix, Bristol-Meyers Squibb, Cara Therapeutics, Celgene, Clinical Outcome Solutions, Concert, DBV, Dermavant, Dermira, Douglas Pharmaceutical, DS Biopharma, Eli Lilly, EMD Serono, Evelo Bioscience, Evidera, FIDE, Galderma, GSK, Haus Bioceuticals, Ichnos Sciences, Incyte, Kyowa Kirin, Larrk Bio, Leo Pharma, Medicxi, Medscape, Neuralstem, Noble Insights, Novan, Novartis, Okava Pharmaceuticals, Pandion Therapeutics, Pfizer, Principia Biopharma, RAPT Therapeutics, Realm, Regeneron Pharmaceuticals, Inc., Sanofi, SATO Pharmaceutical, Sienna Biopharma, Seanegy Dermatology, Seelos Therapeutics, Serpin Pharma, Siolta Therapeutics, Sonoma Biotherapeutics, Sun Pharma, Target PharmaSolutions and Union Therapeutics, Vanda Pharmaceuticals, Ventyx Biosciences, and Vimalan. No other disclosures were reported.
(© 2021 Nakamizo et al.)