Immunity | Li Wei/Yao Xu and other teams discovered that different human Langerhans cell subgroups coordinate their functions with each other

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iNatureLangerhans cells (LCs) play a key role in skin homeostasis, but the cellular and functional heterogeneity of LCs remains elusive
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September 10, 2021, Li Wei, Fudan University, Yao Xu, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, and Li Xiao, Texas Heart Institute (The Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College is the first Unit) Joint Communication published a research paper titled "Distinct human Langerhans cell subsets orchestrate reciprocal functions and require different developmental regulation" in Immunity.
The study used single-cell RNA sequencing and mass spectrometry to identify human skin epidermis and CD34+ hematopoietic stem cells ( HSC-LC) two steady-state (LC1 and LC2) and two activated LC cell subpopulations in the LC
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Analysis of HSC-LC at multiple time points in the differentiation process showed that EGR1 and Notch signals are one of the main ways to regulate the bifurcation of LC1 and LC2
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LC1 is characterized as classical LC, which is mainly related to innate immunity and antigen processing
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LC2 is similar to monocytes or myeloid dendritic cells and participates in immune response and white blood cell activation
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LC1 remains stable in the inflammatory microenvironment, while LC2 is easily activated and exhibits increased expression of immunosuppressive molecules
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The study revealed different subsets of human LC, which require different developmental regulation and coordination of each other's functions
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Langerhans cells (LC) have multiple functions in skin homeostasis and can induce immunogenic or tolerogenic responses
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Although LC is associated with a variety of inflammatory skin diseases, including psoriasis and atopic dermatitis, the role of LC in these diseases is still controversial
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A reasonable explanation is that LC contains a subset of multiple functions that can coordinate and fine-tune the immune response
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However, the cellular and functional heterogeneity of LC remains elusive
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LC shows a mixture of macrophages and dendritic cells (DC), so it has recently been described as "dendritic cell-coated macrophages
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 LC replenishes itself in the epidermis at rest, but refills with bone marrow-derived precursors in inflamed skin
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Studies using mouse models have shown that the differentiation of LC depends on several transforming growth factor β (TGF-β) signaling-related transcription factors, such as PU.
1, RUNX3 and ID2, and CSF1R and interleukin 34 (IL-34).
Interaction
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Notch signal has also been shown to promote LC differentiation
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However, the full scope of the ontogeny and differentiation regulation of human LC is far from being understood
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The article pattern (picture from Immunity) is here.
This study attempts to explore the heterogeneity of human LC through single-cell RNA sequencing (scRNA-seq) and mass spectrometry flow cytometry
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This study identified LC subgroups with different phenotypes in human skin epidermis, and described the complete differentiation trajectory of LC derived from cord blood CD34+ hematopoietic stem cells (HSC-LC)
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The study discovered key transcription factors that regulate differentiation and analyzed the different functions of LC subgroups
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Therefore, this study reports a single-cell resolution map of the development and heterogeneous functions of human LC
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