RARα supports the development of Langerhans cells and langerin-expressing conventional dendritic cells
Open accessAbstract
Langerhans cells (LC) are the prototype langerin-expressing dendritic cells (DC) that reside specifically in the epidermis, but langerin-expressing conventional DCs also reside in the dermis and other tissues, yet the factors that regulate their development are unclear. Because retinoic acid receptor alpha (RARα) is highly expressed by LCs, we investigate the functions of RARα and retinoic acid (RA) in regulating the langerin-expressing DCs. Here we show that the development of LCs from embryonic and bone marrow-derived progenitors and langerin + conventional DCs is profoundly regulated by the RARα-RA axis. During LC differentiation, RARα is required for the expression of a LC-promoting transcription factor Runx3, but suppresses that of LC-inhibiting C/EBPβ. RARα promotes the development of LCs and langerin + conventional DCs only in hypo-RA conditions, a function effectively suppressed at systemic RA levels. Our findings identify positive and negative regulatory mechanisms to tightly regulate the development of the specialized DC populations.
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Recent studies have highlighted the critical role of RA in the derivation of embryonic hematopoietic cells, lymphoid organs, and Langerhans cells that reside specifically in the epidermis.
“Besides the neurogenic potential of RA, recent studies have highlighted the critical role of RA in the derivation of embryonic hematopoietic cells9, lymphoid organs13, and Langerhans cells that reside specifically in the epidermis16.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [16]
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References 55 · Cited by 24
- Authors
- Hashimoto-Hill, S., Friesen, L., Park, S., Im, S., Kaplan, M. H., & Kim, C. H.
- Affiliations
- Purdue University West Lafayette (US)
- Indiana University School of Medicine (US)
- University of Michigan (US)
- Corresponding author
- Kim, Chang H.
- Venue
- Nature Communications
- Published
- 2018-09-25
- Volume
- 9
- Issue
- 1
- Pages
- 3896-3896
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6156335
- OpenAlex
- W2891401984
- Cited by
- 24
- References
- 55
- Citations by year
- 2026: 3 · 2024: 5 · 2023: 1 · 2022: 3 · 2021: 8 · 2020: 3 · 2019: 1
- FWCI
- 1.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- IUScholarWorks (Indiana University) (submittedVersion, cc-by-nc-nd)
- Purdue University Indianapolis (Indiana University) (submittedVersion, cc-by-nc-nd)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (R01DK076616)
- U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (R01AI080769)
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases (R01AI121302)
- National Institute of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- retinoic acid receptor alpha, retinoic acid, Langerhans cells, dendritic cell development, RUNX3, C/EBPβ, epidermal Langerhans cells, bone marrow-derived progenitors, transcriptional regulation
- MeSH terms
- Retinoic Acid Receptor alpha, Animals, Antigens, Surface, Bone Marrow Cells, Cell Differentiation, Cells, Cultured, Dendritic Cells, Humans, Langerhans Cells, Mice, Inbred C57BL, Mice, Transgenic, Mice, Knockout, Gene Expression Profiling, CCAAT-Enhancer-Binding Protein-beta, Lectins, C-Type, Mannose-Binding Lectins, Core Binding Factor Alpha 3 Subunit
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