Cited by 116Mast cells and histamineVitamin D Research StudiesSkin Protection and Aging

Evidence that vitamin D3 promotes mast cell–dependent reduction of chronic UVB-induced skin pathology in mice

Open access
Biggs, Lisa, Yu, Chunping, Fedoric, Boris, Lopez, Angel F., Galli, Stephen J., Grimbaldeston, Michele A.·2010·Journal of Experimental Medicine

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1084/jem.20091725

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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 measured
  • UVR 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)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 29

  1. Alard P. Niizeki H. Hanninen L. Streilein J.W. 1999 Local ultraviolet B irradiation impairs contact hypersensitivity induction by triggering release of tumor necrosis factor-alpha from mast cells. Involvement of mast cells and Langerhans cells in susceptibility to ultraviolet B. J. Invest. Dermatol. 113: 983– 990 10.1046/j.1523-1747.1999.00772.x 10594741 · DOI
  2. Baroni E. Biffi M. Benigni F. Monno A. Carlucci D. Carmeliet G. Bouillon R. D’Ambrosio D. 2007 VDR-dependent regulation of mast cell maturation mediated by 1,25-dihydroxyvitamin D3. J. Leukoc. Biol. 81: 250– 262 10.1189/jlb.0506322 17035339 · DOI
  3. Beissert S. Schwarz A. Schwarz T. 2006 Regulatory T cells. J. Invest. Dermatol. 126: 15– 24 10.1038/sj.jid.5700004 16417213 · DOI
  4. Boonstra A. Barrat F.J. Crain C. Heath V.L. Savelkoul H.F. O’Garra A. 2001 1α,25-Dihydroxyvitamin D3 has a direct effect on naive CD4+ T cells to enhance the development of Th2 cells. J. Immunol. 167: 4974– 4980 11673504
  5. Bouillon R. Carmeliet G. Verlinden L. van Etten E. Verstuyf A. Luderer H.F. Lieben L. Mathieu C. Demay M. 2008 Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29: 726– 776 10.1210/er.2008-0004 18694980 PMC2583388 · DOI · Paper page
  6. Chervenick P.A. Boggs D.R. 1969 Decreased neutrophils and megakaryocytes in anemic mice of genotype W/Wv. J. Cell. Physiol. 73: 25– 30 10.1002/jcp.1040730104 5765776 · DOI
  7. Ellison T.I. Smith M.K. Gilliam A.C. MacDonald P.N. 2008 Inactivation of the vitamin D receptor enhances susceptibility of murine skin to UV-induced tumorigenesis. J. Invest. Dermatol. 128: 2508– 2517 10.1038/jid.2008.131 18509362 PMC4127033 · DOI · Paper page
  8. Galli S.J. Grimbaldeston M. Tsai M. 2008 Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat. Rev. Immunol. 8: 478– 486 10.1038/nri2327 18483499 PMC2855166 · DOI
  9. Galli S.J. Kalesnikoff J. Grimbaldeston M.A. Piliponsky A.M. Williams C.M. Tsai M. 2005 Mast cells as “tunable” effector and immunoregulatory cells: recent advances. Annu. Rev. Immunol. 23: 749– 786 10.1146/annurev.immunol.21.120601.141025 15771585 · DOI
  10. Gorman S. Kuritzky L.A. Judge M.A. Dixon K.M. McGlade J.P. Mason R.S. Finlay-Jones J.J. Hart P.H. 2007 Topically applied 1,25-dihydroxyvitamin D3 enhances the suppressive activity of CD4+CD25+ cells in the draining lymph nodes. J. Immunol. 179: 6273– 6283 17947703
  11. Grimbaldeston M.A. Nakae S. Kalesnikoff J. Tsai M. Galli S.J. 2007 Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat. Immunol. 8: 1095– 1104 17767162
  12. Hart P.H. Grimbaldeston M.A. Swift G.J. Hosszu E.K. Finlay-Jones J.J. 1999 A critical role for dermal mast cells in cis-urocanic acid-induced systemic suppression of contact hypersensitivity responses in mice. Photochem. Photobiol. 70: 807– 812 10.1111/j.1751-1097.1999.tb08286.x 10568173 · DOI
  13. Hart P.H. Grimbaldeston M.A. Swift G.J. Jaksic A. Noonan F.P. Finlay-Jones J.J. 1998 Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. J. Exp. Med. 187: 2045– 2053 10.1084/jem.187.12.2045 9625764 PMC2212357 · DOI · Paper page
  14. Hart P.H. Townley S.L. Grimbaldeston M.A. Khalil Z. Finlay-Jones J.J. 2002 Mast cells, neuropeptides, histamine, and prostaglandins in UV-induced systemic immunosuppression. Methods. 28: 79– 89 10.1016/S1046-2023(02)00201-3 12231191 · DOI · Paper page
  15. Kato S. Kim M.S. Yamaoka K. Fujiki R. 2007 Mechanisms of transcriptional repression by 1,25(OH)2 vitamin D. Curr. Opin. Nephrol. Hypertens. 16: 297– 304 10.1097/MNH.0b013e3281c55f16 17565270 · DOI
  16. Khalil Z. Townley S.L. Grimbaldeston M.A. Finlay-Jones J.J. Hart P.H. 2001 cis-Urocanic acid stimulates neuropeptide release from peripheral sensory nerves. J. Invest. Dermatol. 117: 886– 891 10.1046/j.0022-202x.2001.01466.x 11676828 · DOI
  17. Kirnbauer R. Köck A. Neuner P. Förster E. Krutmann J. Urbanski A. Schauer E. Ansel J.C. Schwarz T. Luger T.A. 1991 Regulation of epidermal cell interleukin-6 production by UV light and corticosteroids. J. Invest. Dermatol. 96: 484– 489 10.1111/1523-1747.ep12470181 2007786 · DOI
  18. Kligman L.H. 1996 The hairless mouse model for photoaging. Clin. Dermatol. 14: 183– 195 10.1016/0738-081X(95)00154-8 9117985 · DOI
  19. Lehmann B. 2005 The vitamin D3 pathway in human skin and its role for regulation of biological processes. Photochem. Photobiol. 81: 1246– 1251 10.1562/2005-02-02-IR-430 16162035 · DOI
  20. Lu L.F. Lind E.F. Gondek D.C. Bennett K.A. Gleeson M.W. Pino-Lagos K. Scott Z.A. Coyle A.J. Reed J.L. Van Snick J. 2006 Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 442: 997– 1002 16921386
  21. Melnikova V.O. Ananthaswamy H.N. 2005 Cellular and molecular events leading to the development of skin cancer. Mutat. Res. 571: 91– 106 15748641
  22. Nigrovic P.A. Gray D.H. Jones T. Hallgren J. Kuo F.C. Chaletzky B. Gurish M. Mathis D. Benoist C. Lee D.M. 2008 Genetic inversion in mast cell-deficient (Wsh) mice interrupts Corin and manifests as hematopoietic and cardiac aberrancy. Am. J. Pathol. 173: 1693– 1701 10.2353/ajpath.2008.080407 18988802 PMC2626381 · DOI
  23. Nishigori C. Yarosh D.B. Ullrich S.E. Vink A.A. Bucana C.D. Roza L. Kripke M.L. 1996 Evidence that DNA damage triggers interleukin 10 cytokine production in UV-irradiated murine keratinocytes. Proc. Natl. Acad. Sci. USA. 93: 10354– 10359 10.1073/pnas.93.19.10354 8816804 PMC38388 · DOI
  24. Noonan F.P. De Fabo E.C. 1992 Immunosuppression by ultraviolet B radiation: initiation by urocanic acid. Immunol. Today. 13: 250– 254 10.1016/0167-5699(92)90005-R 1388651 · DOI
  25. Piliponsky A.M. Chen C.-C. Grimbaldeston M.A. Burns-Guydish S.M. Hardy J.W. Kalesnikoff J. Contag C.H. Tsai M. Galli S.J. 2010 Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6-KitW-sh/W-sh mice. Am. J. Pathol. 176: 926– 938 10.2353/ajpath.2010.090342 20035049 PMC2808097 · DOI
  26. Townley S.L. Grimbaldeston M.A. Ferguson I. Rush R.A. Zhang S.H. Zhou X.F. Conner J.M. Finlay-Jones J.J. Hart P.H. 2002 Nerve growth factor, neuropeptides, and mast cells in ultraviolet-B-induced systemic suppression of contact hypersensitivity responses in mice. J. Invest. Dermatol. 118: 396– 401 10.1046/j.0022-202x.2001.01679.x 11874476 · DOI
  27. van Etten E. Mathieu C. 2005 Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J. Steroid Biochem. Mol. Biol. 97: 93– 101 16046118
  28. Wolf P. Maier H. Müllegger R.R. Chadwick C.A. Hofmann-Wellenhof R. Soyer H.P. Hofer A. Smolle J. Horn M. Cerroni L. 2000 Topical treatment with liposomes containing T4 endonuclease V protects human skin in vivo from ultraviolet-induced upregulation of interleukin-10 and tumor necrosis factor-alpha. J. Invest. Dermatol. 114: 149– 156 10.1046/j.1523-1747.2000.00839.x 10620131 · DOI
  29. Yamazaki F. Okamoto H. Miyauchi-Hashimoto H. Matsumura Y. Itoh T. Tanaka K. Kunisada T. Horio T. 2004 XPA gene-deficient, SCF-transgenic mice with epidermal melanin are resistant to UV-induced carcinogenesis. J. Invest. Dermatol. 123: 220– 228 10.1111/j.0022-202X.2004.22710.x 15191564 · DOI

Cited by

Sorted by citations

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
Published
2010-03-01
Volume
207
Issue
3
Pages
455-463
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
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
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

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.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review