1. Immunology and Inflammation
Download icon

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
Research Article
  • Cited 0
  • Views 326
  • Annotations
Cite this article as: eLife 2021;10:e65412 doi: 10.7554/eLife.65412

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.

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.

Reviewing Editor

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

Publication history

  1. Received: December 3, 2020
  2. Accepted: March 25, 2021
  3. Accepted Manuscript published: March 26, 2021 (version 1)

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.

Metrics

  • 326
    Page views
  • 74
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease
    Philipp Kolb et al.
    Research Article Updated

    Human cytomegalovirus (HCMV) is endowed with multiple highly sophisticated immune evasion strategies. This includes the evasion from antibody mediated immune control by counteracting host Fc-gamma receptor (FcγR) mediated immune control mechanisms such as antibody-dependent cellular cytotoxicity (ADCC). We have previously shown that HCMV avoids FcγR activation by concomitant expression of the viral Fc-gamma-binding glycoproteins (vFcγRs) gp34 and gp68. We now show that gp34 and gp68 bind IgG simultaneously at topologically different Fcγ sites and achieve efficient antagonization of host FcγR activation by distinct but synergizing mechanisms. While gp34 enhances immune complex internalization, gp68 acts as inhibitor of host FcγR binding to immune complexes. In doing so, gp68 induces Fcγ accessibility to gp34 and simultaneously limits host FcγR recognition. The synergy of gp34 and gp68 is compelled by the interfering influence of excessive non-immune IgG ligands and highlights conformational changes within the IgG globular chains critical for antibody effector function.

    1. Cell Biology
    2. Immunology and Inflammation
    Shannon M Walsh et al.
    Tools and Resources

    The detection of foreign antigens in vivo has relied on fluorescent conjugation or indirect read-outs such as antigen presentation. In our studies, we found that these widely used techniques had several technical limitations that have precluded a complete picture of antigen trafficking or retention across lymph node cell types. To address these limitations, we developed a 'molecular tracking device' to follow the distribution, acquisition, and retention of antigen in the lymph node. Utilizing an antigen conjugated to a nuclease-resistant DNA tag, acting as a combined antigen-adjuvant conjugate, and single-cell mRNA sequencing we quantified antigen abundance in lymph node. Variable antigen levels enabled the identification of caveolar endocytosis as a mechanism of antigen acquisition or retention in lymphatic endothelial cells. Thus, these molecular tracking devices enable new approaches to study dynamic tissue dissemination of antigen-adjuvant conjugates and identify new mechanisms of antigen acquisition and retention at cellular resolution in vivo.