Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac–derived macrophages
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Langerhans cells (LCs) are the dendritic cells (DCs) of the epidermis, forming one of the first hematopoietic lines of defense against skin pathogens. In contrast to other DCs, LCs arise from hematopoietic precursors that seed the skin before birth. However, the origin of these embryonic precursors remains unclear. Using in vivo lineage tracing, we identify a first wave of yolk sac (YS)–derived primitive myeloid progenitors that seed the skin before the onset of fetal liver hematopoiesis. YS progenitors migrate to the embryo proper, including the prospective skin, where they give rise to LC precursors, and the brain rudiment, where they give rise to microglial cells. However, in contrast to microglia, which remain of YS origin throughout life, YS-derived LC precursors are largely replaced by fetal liver monocytes during late embryogenesis. Consequently, adult LCs derive predominantly from fetal liver monocyte-derived cells with a minor contribution of YS-derived cells. Altogether, we establish that adult LCs have a dual origin, bridging early embryonic and late fetal myeloid development.
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On day 115 of differentiation (≈16-week of embryonic development), the presence of CD207+ immune cells in the dermal region suggests two possibilities: migration of Langerhans cell precursors from the dermis, or presence of dermal dendritic cells, both of which express CD207+.
“On day 115 of differentiation (≈16‐week of embryonic development), the presence of CD207+ immune cells in the dermal region suggests two possibilities: first, the migration of Langerhans cell precursors from the dermis[ 82 , 83 ]; and second, the presence of dermal dendritic cells,[ 82 , 83 ] both of which express CD207+.”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [82]
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- Authors
- Hoeffel, G., Wang, Y., Greter, M., See, P., Teo, P., Malleret, B., Leboeuf, M., Low, D., Oller, G., Almeida, F., Choy, S. H. Y., Grisotto, M., Renia, L., Conway, S. J., Stanley, E. R., Chan, J. K. Y., Ng, L. G., Samokhvalov, I. M., Merad, M., & Ginhoux, F.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Icahn School of Medicine at Mount Sinai (US)
- Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Immunos Building #3-4, BIOPOLIS, 138648, Singapore 1
- Universidade Ceuma (BR)
- Indiana University Indianapolis (US)
- Albert Einstein College of Medicine (US)
- National University of Singapore (SG)
- RIKEN (JP)
- Department of Gene and Cell Medicine 2 and 3
- Corresponding author
- Ginhoux, Florent
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2012-05-07
- Volume
- 209
- Issue
- 6
- Pages
- 1167-1181
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC3371735
- OpenAlex
- W2124841332
- Cited by
- 786
- References
- 7
- Citations by year
- 2026: 26 · 2025: 34 · 2024: 55 · 2023: 39 · 2022: 41 · 2021: 53 · 2020: 58 · 2019: 59 · 2018: 70 · 2017: 67 · 2016: 70 · 2015: 78 · 2014: 79 · 2013: 46 · 2012: 11
- FWCI
- 29.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-sa)
- Funders
- National Science Foundation
- National University of Singapore
- National Institutes of Health (CA32551, CA26504)
- National Medical Research Council (CSA/012/2009)
- RIKEN
- National Heart, Lung, and Blood Institute (HL086899, R01HL086899)
- National Cancer Institute (CA-32551, R01CA032551, R37CA026504, R01CA112100, CA26504, CA112100, R01CA026504, R01CA154947)
- National Institute of Allergy and Infectious Diseases (U01AI095611, AI080884, R01AI080884)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- Langerhans cells, dendritic cells, cell of origin, lineage tracing, epidermis, myeloid development
- MeSH terms
- Age Factors, Animals, Female, Langerhans Cells, Liver, Macrophages, Mice, Inbred C57BL, Monocytes, Pregnancy, Skin, Stem Cells, Yolk Sac, Microglia, Cell Lineage, Myeloid Progenitor Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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