Evidence that vitamin D3 promotes mast cell–dependent reduction of chronic UVB-induced skin pathology in mice
Open accessAbstract
Mast cell production of interleukin-10 (IL-10) can limit the skin pathology induced by chronic low-dose ultraviolet (UV)-B irradiation. Although the mechanism that promotes mast cell IL-10 production in this setting is unknown, exposure of the skin to UVB irradiation induces increased production of the immune modifying agent 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3). We now show that 1α,25(OH)2D3 can up-regulate IL-10 mRNA expression and induce IL-10 secretion in mouse mast cells in vitro. To investigate the roles of 1α,25(OH)2D3 and mast cell vitamin D receptor (VDR) expression in chronically UVB-irradiated skin in vivo, we engrafted the skin of genetically mast cell–deficient WBB6F1-KitW/W-v mice with bone marrow–derived cultured mast cells derived from C57BL/6 wild-type or VDR−/− mice. Optimal mast cell–dependent suppression of the inflammation, local production of proinflammatory cytokines, epidermal hyperplasia, and epidermal ulceration associated with chronic UVB irradiation of the skin in KitW/W-v mice required expression of VDR by the adoptively transferred mast cells. Our findings suggest that 1α,25(OH)2D3/VDR-dependent induction of IL-10 production by cutaneous mast cells can contribute to the mast cell’s ability to suppress inflammation and skin pathology at sites of chronic UVB irradiation.
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UV radiation and topical 1,25(OH)2D3 can activate dermal mast cells, which are important to determine the extent of UV immunomodulation.
“For example, UV radiation and topical 1,25(OH)2D3 can also activate dermal mast cells [88,89], which are important to determine the extent of UV immunomodulation [89,90].”
From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [88]
The Results and Discussion (page not provided) suggest that UVB-induced 1α,25(OH)2D3 contributes to dermal mast-cell activation and show that mast cells affect inflammatory cytokines and skin pathology after chronic UVB exposure in mice. The paper does not report topical application of 1,25(OH)2D3 or establish its effect on the extent of UV-induced immunomodulation more generally. (LLM, conf=0.86)
Experimental — accuracy not yet measuredUVR radiation and topical 1,25(OH)2D3 can activate dermal mast cells.
“In mast cells, UVR radiation and topical 1,25(OH)2D3 can also activate dermal mast cells [88,89]”
From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [88]
The Results and Discussion section says UVB irradiation increases skin levels of 1α,25(OH)2D3 and suggests that the metabolite contributes to dermal mast-cell activation. The Materials and Methods section describes applying 1α,25(OH)2D3 to cultured mast cells, not topically to skin; topical application is therefore unsupported by this paper. Page numbers are not available in our copy. (LLM, conf=0.86)
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Cites
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“, 2005) or inflammation caused by innate responses to exogenous environmental agents such as UV irradiation (Metz et al., 2006), recent evidence indicates that, in certain settings, mast cells can also limit inflammation and tissue injury, including that induced by UVB irradiation (Grimbaldeston et al.”
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Cited by
Sorted by citations
Galli, S. J., & Tsai, M. (2010) · European Journal of Immunology · doi:10.1002/eji.201040559 · Cited by 403 · see citing works
Self-citationLee, C.-H., Wu, S.-B., Hong, C.-H., Yu, H.-S., & Wei, Y.-H. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14036414 · Cited by 271 · see citing works
Meningeal mast cells as key effectors of stroke pathology.
Arac, A., Grimbaldeston, M. A., Galli, S. J., Bliss, T. M., & Steinberg, G. K. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00126 · Cited by 37 · see citing works
Self-citation
- Authors
- Biggs, L., Yu, C., Fedoric, B., Lopez, A. F., Galli, S. J., & Grimbaldeston, M. A.
- Affiliations
- Centre for Cancer Biology (AU)
- Stanford Medicine (US)
- Corresponding author
- Galli, Stephen J.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2010-03-01
- Volume
- 207
- Issue
- 3
- Pages
- 455-463
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2839149
- OpenAlex
- W2067550159
- Cited by
- 116
- References
- 2
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 1 · 2023: 3 · 2022: 8 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 9 · 2016: 8 · 2015: 9 · 2014: 8 · 2013: 11 · 2012: 12
- FWCI
- 5.91
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- National Cancer Institute (R01CA072074, CA 72074)
- National Institute of Allergy and Infectious Diseases (AI-070813, R01AI023990, R01AI070813, R37AI023990, AI-23990)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- vitamin D3, 1,25-dihydroxyvitamin D3, vitamin D receptor, mast cells, IL-10, epidermal hyperplasia, epidermal ulceration, mast cell-deficient mice, inflammatory cytokines, immunomodulation
- MeSH terms
- Animals, Bone Marrow Cells, Calcitriol, Cells, Cultured, Cholecalciferol, Inflammation, Mast Cells, Mice, Inbred C57BL, Pigmentation, Radiography, Skin, Ultraviolet Rays, Skin Transplantation, Cytokines, Interleukin-10, Receptors, Calcitriol, Mice, Knockout, Cell Culture Techniques, Mice
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