Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population
- Zhejiang University School of Medicine, China
- Nanyang Technological University, Singapore
- Malaghan Institute of Medical Research, New Zealand
- 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.
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Langerhans cell RNAseqNCBI Gene Expression Omnibus, GSE139877.
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Langerhans cells do not migrate to draining lymph nodesNCBI Bioproject, PRJNA625270.
Article and author information
Author details
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
- 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
- Received: December 3, 2020
- Accepted: March 25, 2021
- Accepted Manuscript published: March 26, 2021 (version 1)
- 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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Fate mapping analysis reveals a novel murine dermal migratory Langerhans-like cell population
eLife 10:e65412.
https://doi.org/10.7554/eLife.65412
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