Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

doi:10.1016/j.immuni.2021.08.012

. 2021 Oct 12;54(10):2305-2320.e11.

doi: 10.1016/j.immuni.2021.08.012. Epub 2021 Sep 10.

Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

Xiaochun Liu¹, Ronghui Zhu², Yang Luo¹, Shangshang Wang², Yi Zhao³, Zhuoqiong Qiu², Yu Zhang¹, Xiao Liu⁴, Xu Yao⁵, Xiao Li⁶, Wei Li⁷

Affiliations

¹ Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
² Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
³ Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁴ Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518052, China.
⁵ Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Electronic address: dryao_xu@126.com.
⁶ Gene Editing Laboratory, Texas Heart Institute, Houston, Texas 77030, USA. Electronic address: xli@texasheart.org.
⁷ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: liweiderma@fudan.edu.cn.

PMID: 34508661
DOI: 10.1016/j.immuni.2021.08.012

Free article

Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

Xiaochun Liu et al. Immunity. 2021.

Free article

. 2021 Oct 12;54(10):2305-2320.e11.

doi: 10.1016/j.immuni.2021.08.012. Epub 2021 Sep 10.

Authors

Xiaochun Liu¹, Ronghui Zhu², Yang Luo¹, Shangshang Wang², Yi Zhao³, Zhuoqiong Qiu², Yu Zhang¹, Xiao Liu⁴, Xu Yao⁵, Xiao Li⁶, Wei Li⁷

Affiliations

¹ Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China.
² Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China.
³ Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁴ Tsinghua Shenzhen International Graduate School, Tsinghua University, Shenzhen 518052, China.
⁵ Department of Allergy and Rheumatology, Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital for Skin Diseases, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China. Electronic address: dryao_xu@126.com.
⁶ Gene Editing Laboratory, Texas Heart Institute, Houston, Texas 77030, USA. Electronic address: xli@texasheart.org.
⁷ Department of Dermatology, Huashan Hospital, Fudan University, Shanghai 200040, China. Electronic address: liweiderma@fudan.edu.cn.

PMID: 34508661
DOI: 10.1016/j.immuni.2021.08.012

Abstract

Langerhans cells (LCs) play a pivotal role in skin homeostasis, and the heterogeneity of LCs has long been considered. In this study, we have identified two steady-state (LC1 and LC2) and two activated LC subsets in the epidermis of human skin and in LCs derived from CD34⁺ hemopoietic stem cells (HSC-LCs) by utilizing single-cell RNA sequencing and mass cytometry. Analysis of HSC-LCs at multiple time-points during differentiation revealed that EGR1 and Notch signaling were among the top pathways regulating the bifurcation of LC1 and LC2. LC1 were characterized as classical LCs, mainly related to innate immunity and antigen processing. LC2 were similar to monocytes or myeloid dendritic cells, involving in immune responses and leukocyte activation. LC1 remained stable under inflammatory microenvironment, whereas LC2 were prone to being activated and demonstrated elevated expression of immuno-suppressive molecules. We revealed distinct human LC subsets that require different developmental regulation and orchestrate reciprocal functions.

Keywords: Langerhans cells; differentiation; function; heterogeneity; human; mass cytometry; phenotype; single-cell RNA sequencing.

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Conflict of interest statement

Declaration of Interests The authors declare no competing interests.

Comment in

Many Langerhans make light work of skin immunity.
Collin M, Bigley V. Collin M, et al. Immunity. 2021 Oct 12;54(10):2188-2190. doi: 10.1016/j.immuni.2021.09.006. Immunity. 2021. PMID: 34644554
Defining the landscape of human epidermal mononuclear phagocytes.
Bertram KM, O'Neil TR, Vine EE, Baharlou H, Cunningham AL, Harman AN. Bertram KM, et al. Immunity. 2023 Mar 14;56(3):459-460. doi: 10.1016/j.immuni.2023.02.001. Immunity. 2023. PMID: 36921567 No abstract available.
Response to identifying the epidermal dendritic cell landscape.
Zhu R, Liu X, Li X, Yao X, Li W. Zhu R, et al. Immunity. 2023 Mar 14;56(3):461-462. doi: 10.1016/j.immuni.2023.02.006. Immunity. 2023. PMID: 36921568 No abstract available.

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Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

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Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation

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