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Langerhans cell origin and regulation
Open accessAbstract
PURPOSE OF REVIEW: This article summarizes recent research on the ontogeny of Langerhans cells and regulation of their homeostasis in quiescent and inflamed conditions. RECENT FINDINGS: Langerhans cells originate prenatally and may endure throughout life, independently of bone marrow-derived precursors. Fate-mapping experiments have recently resolved the relative contribution of primitive yolk sac and fetal liver hematopoiesis to the initial formation of Langerhans cells. In postnatal life, local self-renewal restores Langerhans cell numbers following chronic or low-grade inflammatory insults. However, severe inflammation recruits de-novo bone marrow-derived precursors in two waves; a transient population of classical monocytes followed by uncharacterized myeloid precursors that form a stable self-renewing Langerhans cell network as inflammation subsides. Human CD1c⁺ dendritic cells have Langerhans cell potential in vitro, raising the possibility that dendritic cell progenitors provide the second wave. Langerhans cell development depends upon transforming growth factor beta receptor signaling with distinct pathways active during differentiation and homeostasis. Langerhans cell survival is mediated by multiple pathways including mechanistic target of rapamycin and extracellular signal-regulated kinase signaling, mechanisms that become highly relevant in Langerhans cell neoplasia. SUMMARY: The study of Langerhans cells continues to provide novel and unexpected insights into the origin and regulation of myeloid cell populations. The melding of macrophage and dendritic cell biology, shaped by a unique habitat, is a special feature of Langerhans cells.
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“Langerhans cells are a unique cell population to the skin organ, where fate‐mapping of macrophages demonstrates in situ proliferation to Langerhans cells in the skin during embryonic development.[ 78 , 79 , 80 , 81 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [78]
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“Mechanistically, this is driven by interleukin‐34 release via macrophage‐colony stimulating factor receptor.[ 78 ]”
From Coordinated Development of Immune Cell Populations in Vascularized Skin Organoids from Human Induced Pluripotent Stem Cells (2025) · cites this paper as [78]
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“Notably, this observation aligns with previous studies that mature human SKOs resemble human fetal craniofacial skin at 18‐week of gestation.[ 26 , 78 ]”
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Metadata
- Authors
- Collin, M., & Milne, P.
- Affiliations
- Newcastle University (GB)
- Corresponding author
- Collin, Matthew
- Venue
- Current Opinion in Hematology
- Published
- 2016-01
- Volume
- 23
- Issue
- 1
- Pages
- 28-35
- ISSN
- 1065-6251 (ISSN-L)
- PMC
- PMC4685746
- OpenAlex
- W2409593987
- Cited by
- 120
- References
- 65
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 12 · 2021: 16 · 2020: 14 · 2019: 13 · 2018: 12 · 2017: 10 · 2016: 6
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Current Opinion in Hematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- Histiocytosis Association
- Wellcome Trust
- Topics
- Health Sciences › Medicine › Hematology › Histiocytic Disorders and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Keywords
- Langerhans cells, fetal liver hematopoiesis, yolk sac hematopoiesis, self-renewal, inflammation, classical monocytes, myeloid precursors, CD1c+ dendritic cells, dendritic cell progenitors, mTOR signaling, ERK signaling, myeloid cell development
- MeSH terms
- Cell Self Renewal, Animals, Cell Differentiation, Fetus, Histiocytosis, Langerhans-Cell, Homeostasis, Humans, Inflammation, Langerhans Cells, Liver, Macrophages, Monocytes, Stem Cells, Yolk Sac, Cell Lineage
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