The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Stroma-Derived Interleukin-34 Controls the Development and Maintenance of Langerhans Cells and the Maintenance of Microglia
Open accessAbstract
Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (IL-34), an alternative ligand for Csf-1 receptor, is produced by keratinocytes in the epidermis and by neurons in the brain. Mice lacking IL-34 displayed a marked reduction of LCs and a decrease of microglia, whereas monocytes, dermal, and lymphoid tissue macrophages and DCs were unaffected. We identified IL-34 as a nonredundant cytokine for the development of LCs during embryogenesis as well as for their homeostasis in the adult skin. Whereas inflammation-induced repopulation of LCs appears to be dependent on Csf-1, once inflammation is resolved, LC survival is again IL-34-dependent. In contrast, microglia and their yolk sac precursors develop independently of IL-34 but rely on it for their maintenance in the adult brain.
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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 [81]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“In the brain, interleukin-34 (IL-34) is an alternative CSF1R ligand supporting microglia survival and differentiation (Greter et al., 2012), and microglia adopt an increasingly ramified morphology and continued maturation far beyond birth.”
From A highly efficient human pluripotent stem cell microglia model displays a neuronal-co-culture-specific expression profile and inflammatory response (2017) · cites this paper as Greter et al., 2012
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In the citing paper
“This lineage is mainly regulated by CSFR14 and its ligand, IL-347.”
From Identification of a unique TGF-β–dependent molecular and functional signature in microglia (2014) · cites this paper as [7]
Experimental — accuracy not yet measuredIn the citing paper
“Several groups have attempted different cell culture conditions to maintain homeostatic microglia signature and ramified morphology In vitro using a variety of cytokines, such as CSF1, GM-CSF, TGFβ, and IL-34 [73-76].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [75]
In the citing paper
“These factors include IL-34 and TGFβ-1 (Butovsky et al., 2014; Greter et al., 2012; Wang et al., 2012; Yamasaki et al., 2014).”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Greter et al., 2012
In the citing paper
“Recently, murine studies identified key cytokines, cell receptors, and transcription factors required for microglia development and survival in vivo.”
From iPSC-derived human microglia-like cells to study neurological diseases (2017) · cites this paper as Greter et al., 2012
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Citations
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Metadata
- Authors
- Greter, M., Lelios, I., Pelczar, P., Hoeffel, G., Price, J., Leboeuf, M., Kündig, T. M., Frei, K., Ginhoux, F., Merad, M., & Becher, B.
- Affiliations
- University of Zurich (CH)
- Agency for Science, Technology and Research (SG)
- Icahn School of Medicine at Mount Sinai (US)
- University Hospital Zurich (CH)
- Corresponding author
- Greter, Melanie
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 37
- Issue
- 6
- Pages
- 1050-1060
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC4291117
- OpenAlex
- W2033985800
- Cited by
- 630
- References
- 28
- Citations by year
- 2026: 35 · 2025: 46 · 2024: 45 · 2023: 40 · 2022: 33 · 2021: 49 · 2020: 56 · 2019: 53 · 2018: 51 · 2017: 52 · 2016: 43 · 2015: 47 · 2014: 49 · 2013: 31
- FWCI
- 20.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Funders
- National Institutes of Health
- Neuroscience Center Zurich, University of Zurich
- National Heart, Lung, and Blood Institute (HL086899, R01HL086899)
- National Cancer Institute (R01CA112100, CA112100)
- National Institute of Allergy and Infectious Diseases (U01AI095611, AI080884, R01AI080884)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- IL-34, Langerhans cells, microglia, CSF-1 receptor, keratinocytes, neurons, macrophage development, embryonic development, skin homeostasis, dendritic cells, monocytes
- MeSH terms
- Animals, Brain, Cell Differentiation, Epidermis, Homeostasis, Humans, Inflammation, Interleukins, Langerhans Cells, Psoriasis, Skin, Signal Transduction, Keratinocytes, Receptor, Macrophage Colony-Stimulating Factor, Stromal Cells, Microglia, Mice
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