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

S Nakamizo, CA Dutertre, A Khalilnezhad… - Journal of Experimental …, 2021 - rupress.org
S Nakamizo, CA Dutertre, A Khalilnezhad, XM Zhang, S Lim, J Lum, G Koh, C Foong…
Journal of Experimental Medicine, 2021rupress.org
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+ …
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.
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