期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 218, 期 9, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20202345
关键词
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资金
- Biomedical Research Council [IAF311006]
- Biomedical Research Council transition funds [H16/99/b0/011]
- European Molecular Biology Organization Young Investigator Promgramme, SIgN core funding (A*STAR)
- A*STAR-NHG-NTU skin research grant [15014]
- SIgN and Skin Research Institute of Singapore
- Japan Society for the Promotion of Science KAKENHI [20H05697, 21K16211]
- Japan Agency for Medical Research and Development [JP21gm1210006]
- Skin Research Institute of Singapore
- Grants-in-Aid for Scientific Research [20H05697, 21K16211] Funding Source: KAKEN
This study reveals the molecular characteristics of different macrophage and DC subsets in AD and PSO through single-cell analysis, identifying CD14(+) DC3 as a potential promoter of inflammation in PSO.
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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