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

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Single-cell analysis of human skin identifies CD14 + type 3 dendritic cells co-producing IL1B and IL23A in psoriasis
Journal of Experimental Medicine ( IF 15.3 ) Pub Date : 2021-07-19 , DOI: 10.1084/jem.20202345
Satoshi Nakamizo _{1,

2,

3} , Charles-Antoine Dutertre _{1,

4,

5} , Ahad Khalilnezhad _{1,

6} , Xiao Meng Zhang ₁ , Shawn Lim ₁ , Josephine Lum ₁ , Geraldine Koh ₁ , Charlene Foong ₇ , Pearly Jean Ai Yong ₇ , Kahbing Jasmine Tan _{1,

2} , Reiko Sato _{1,

3} , Kaori Tomari ₃ , Laurent Yvan-Charvet ₈ , Helen He ₉ , Emma Guttman-Yassky ₉ , Benoit Malleret _{1,

6} , Rintaro Shibuya ₃ , Masashi Iwata ₃ , Baptiste Janela ₂ , Tsuyoshi Goto ₁₀ , Tan Siyun Lucinda ₁₁ , Mark B Y Tang ₁₁ , Colin Theng ₁₁ , Valerie Julia ₁₂ , Feriel Hacini-Rachinel ₁₂ , Kenji Kabashima _{1,

2,

3,

10} , Florent Ginhoux _{1,

2,

5,

13}

Affiliation

Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.
Skin Research Institute of Singapore, Agency for Science, Technology and Research, Singapore.
Department of Dermatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Program in Emerging Infectious Disease, Duke-NUS Medical School, Singapore.
Translational Immunology Institute, Singhealth/Duke-NUS Academic Medical Centre, Singapore.
Department of Microbiology and Immunology, Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore.
SingHealth Flow Cytometry, Singapore.
Institut National de la Santé et de la Recherche Médicale U1065, Centre Mediterraneen de Medecine Moleculaire, Atip-Avenir, Nice, France.
Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY.
Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto, Japan.
National Skin Centre, Singapore.
Galderma, La Tour-de-Peilz, Switzerland.
Shanghai Institute of Immunology, Shanghai JiaoTong University School of Medicine, Shanghai, China.

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.

更新日期：2021-07-20

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