Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population

  1. Jianpeng Sheng  Is a corresponding author
  2. Qi Chen
  3. Xiaoting Wu
  4. Yu Wen Dong
  5. Johannes U Mayer
  6. Junlei Zhang
  7. Lin Wang
  8. Xueli Bai
  9. Tingbo Liang
  10. Yang Ho Sung
  11. Wilson Wen Bin Goh
  12. Franca Ronchese
  13. Christiane Ruedl  Is a corresponding author
  1. Zhejiang University School of Medicine, China
  2. Nanyang Technological University, Singapore
  3. Malaghan Institute of Medical Research, New Zealand
  4. Zhejiang University, China

Abstract

Dendritic cells residing in the skin represent a large family of antigen presenting cells, ranging from long-lived Langerhans cells (LC) in the epidermis to various distinct classical dendritic cell subsets in the dermis. Through genetic fate mapping analysis and single cell RNA sequencing we have identified a novel separate population of LC-independent CD207+CD326+ LClike cells in the dermis that homed at a slow rate to the LNs. These LClike cells are long-lived and radioresistant but, unlike LCs, they are gradually replenished by bone-marrow-derived precursors under steady state. LClike cells together with cDC1s are the main migratory CD207+CD326+ cell fractions present in the LN and not, as currently assumed, LCs, which are barely detectable, if at all. Cutaneous tolerance to haptens depends on LClike cells, whereas LCs suppress effector CD8+ T cell functions and inflammation locally in the skin during contact hypersensitivity. These findings bring new insights into the dynamism of cutaneous dendritic cells and their function opening novel avenues in the development of treatments to cure inflammatory skin disorders.

Data availability

All RNA-sequencing data have been deposited in the Gene Expression Omnibus public database under accession number GSE139877. Single cell RNAseq have been deposited into NCBI SRA database with BioProject ID: PRJNA625270.

The following data sets were generated

Article and author information

Author details

  1. Jianpeng Sheng

    Zhejiang Provincial Key Laboratory of Pancreatic Disease, Zhejiang University School of Medicine, Hangzhou, China
    For correspondence
    JSHENG2@e.ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
  2. Qi Chen

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0658-7629
  3. Xiaoting Wu

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0281-8717
  4. Yu Wen Dong

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  5. Johannes U Mayer

    Malaghan Institute of Medical Research, Malaghan Institute of Medical Research, Wellington, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6225-7803
  6. Junlei Zhang

    Zhejiang University School of Medicine, Zhejiang University School of Medicine, Zhejiang, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Lin Wang

    Zhejiang Provincial Key Laboratory of Pancreatic Disease, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Xueli Bai

    Zhejiang Provincial Key Laboratory of Pancreatic Disease, Zhejiang University School of Medicine, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Tingbo Liang

    Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Yang Ho Sung

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  11. Wilson Wen Bin Goh

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
  12. Franca Ronchese

    Malaghan Institute of Medical Research, Malaghan Institute of Medical Research, Wellington, New Zealand
    Competing interests
    The authors declare that no competing interests exist.
  13. Christiane Ruedl

    School of Biological Sciences, Nanyang Technological University, Singapore, Singapore
    For correspondence
    ruedl@ntu.edu.sg
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5599-6541

Funding

Ministry of Education - Singapore (Tier1)

  • Christiane Ruedl

National Key R&D Program China (2019YFA0803000)

  • Jianpeng Sheng

Health Research Council of New Zealand (Independent Research Organisation grant)

  • Franca Ronchese

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Bernard Malissen, Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université, France

Ethics

Animal experimentation: All studies involving mice in Singapore were carried out in strict accordance with the recommendations of the National Advisory Committee for Laboratory Animal Research and all protocols were approved by the Institutional Animal Care and Use Committee of the Nanyang Technological University (ARF-SBS/NIE A-0133; A-0257; A0126, A-18081). For animal work performed in New Zealand, experimental protocols were approved by the Victoria University of Wellington Animal Ethics Committee and performed in accordance with institutional guidelines.

Version history

  1. Received: December 3, 2020
  2. Accepted: March 25, 2021
  3. Accepted Manuscript published: March 26, 2021 (version 1)
  4. Version of Record published: May 10, 2021 (version 2)

Copyright

© 2021, Sheng et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jianpeng Sheng
  2. Qi Chen
  3. Xiaoting Wu
  4. Yu Wen Dong
  5. Johannes U Mayer
  6. Junlei Zhang
  7. Lin Wang
  8. Xueli Bai
  9. Tingbo Liang
  10. Yang Ho Sung
  11. Wilson Wen Bin Goh
  12. Franca Ronchese
  13. Christiane Ruedl
(2021)
Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population
eLife 10:e65412.
https://doi.org/10.7554/eLife.65412

Share this article

https://doi.org/10.7554/eLife.65412

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