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  • Review Article
  • Published:

Modulation of the immune system by UV radiation: more than just the effects of vitamin D?

Nature Reviews Immunology volume 11, pages 584–596 (2011)Cite this article

Subjects

Key Points

  • Ultraviolet (UV) irradiation of skin and consequent suppression of local and systemic immune responses have been associated with reduced severity of some inflammatory and immune diseases. Vitamin D deficiency has been linked with immune diseases such as multiple sclerosis and allergic asthma. The suppression of immune responses and the induction of antimicrobial peptides by vitamin D may contribute to these associations.

  • Humans obtain most of their vitamin D by exposure of skin to sunlight. The benefits of moderate UV radiation exposure (and positive latitude gradients for diseases) may reflect UV-induced vitamin D production.

  • UV irradiation of skin can affect the manifestation of local diseases (for example, psoriasis) and cause altered responses to topical or intradermal antigens. Vitamin D is a candidate mediator for these effects. However, for the suppression of systemic diseases (such as multiple sclerosis and asthma), the links between UV radiation and UV-induced vitamin D are more equivocal.

  • In multiple sclerosis, further evidence is needed to determine whether the positive latitude gradient for disease prevalence is influenced by UV radiation independently of vitamin D. For allergic asthma, a positive latitude gradient has been recently reported and vitamin D intervention studies have been promising. It is likely that UV irradiation of skin affects human immune outcomes by multiple modulatory pathways, and different stages of disease pathogenesis may vary in their response to UV-induced regulatory molecules and vitamin D.

  • By inducing antimicrobial peptides and exerting immunosuppressive effects, UV radiation and vitamin D may provide an adjunctive therapy for some diseases through microbial control with reduced tissue damage. In addition, vitamin D may modulate the development of innate immune responses through effects on gut flora.

  • Other UV-induced mediators (namely, cis-urocanic acid and oxidation products of DNA, lipids and proteins) may contribute to the consequent systemic immunomodulation following UV irradiation.

Abstract

Humans obtain most of their vitamin D through the exposure of skin to sunlight. The immunoregulatory properties of vitamin D have been demonstrated in studies showing that vitamin D deficiency is associated with poor immune function and increased disease susceptibility. The benefits of moderate ultraviolet (UV) radiation exposure and the positive latitude gradients observed for some immune-mediated diseases may therefore reflect the activities of UV-induced vitamin D. Alternatively, other mediators that are induced by UV radiation may be more important for UV-mediated immunomodulation. Here, we compare and contrast the effects of UV radiation and vitamin D on immune function in immunopathological diseases, such as psoriasis, multiple sclerosis and asthma, and during infection.

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Figure 1: Actions of 1,25-dihydroxyvitamin D3 on human immune cells.
Figure 2: UV-induced mechanisms of immunomodulation.

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References

  1. Kripke, M. L. Antigenicity of murine skin tumors induced by ultraviolet light. J. Natl Cancer Inst. 53, 1333–1336 (1974).

    Article  CAS  PubMed  Google Scholar 

  2. Norval, M. The mechanisms and consequences of ultraviolet-induced immunosuppression. Prog. Biophys. Mol. Biol. 92, 108–118 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Agar, N. S. et al. The basal layer in human squamous tumors harbors more UVA than UVB fingerprint mutations: a role for UVA in human skin carcinogenesis. Proc. Natl Acad. Sci. USA 101, 4954–4959 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Damian, D. L., Matthews, Y. L., Phan, T. A. & Halliday, G. M. An action spectrum for ultraviolet radiation-induced immunosuppression in humans. Br. J. Dermatol. 164, 657–659 (2011).

    CAS  PubMed  Google Scholar 

  5. Reeve, V. E., Allanson, M., Cho, J.-L., Arun, S. J. & Domanski, D. Interdependence between heme oxygenase-1 induction and estrogen-receptor-β signaling mediates photoimmune protection by UVA radiation in mice. J. Invest. Dermatol. 129, 2702–2710 (2009).

    Article  CAS  PubMed  Google Scholar 

  6. Kelly, D. A. et al. Sensitivity to sunburn is associated with susceptibility to ultraviolet radiation-induced suppression of cutaneous cell-mediated immunity. J. Exp. Med. 191, 561–566 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ullrich, S. E. Mechanisms underlying UV-induced immune suppression. Mutat. Res. 571, 185–205 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Norval, M., McLoone, P., Lesiak, A. & Narbutt, J. The effect of chronic ultraviolet radiation on the human immune system. Photochem. Photobiol. 84, 19–28 (2008). In this review, many parameters of immunity are analysed following multiple exposures of human skin to UV radiation, and compared with the consequences of a single acute UV irradiation of skin.

    Article  CAS  PubMed  Google Scholar 

  9. Bouillon, R. et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr. Rev. 29, 726–776 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hewison, M. Vitamin D and the intracrinology of innate immunity. Mol. Cell. Endocrinol. 321, 103–111 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Hewison, M. Antibacterial effects of vitamin D. Nature Rev. Endocrinol. 7, 337–345 (2011).

    Article  CAS  Google Scholar 

  12. Beard, J. A., Bearden, A. & Striker, R. Vitamin D and the anti-viral state. J. Clin. Virol. 50, 194–200 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lehrer, R. I. & Ganz, T. G. Cathelicidins: a family of endogenous antimicrobial peptides. Curr. Opin. Hematol. 9, 18–22 (2002).

    Article  PubMed  Google Scholar 

  14. Liu, P. T. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770–1773 (2006). This was the first study to link TLR receptor triggering in human macrophages with increases in the enzyme responsible for 1,25(OH) 2 D3 synthesis and subsequent production of the antimicrobial peptide cathelicidin. Positive associations between vitamin D levels and killing of intracellular M. tuberculosis were demonstrated.

    Article  CAS  PubMed  Google Scholar 

  15. Edfeldt, K. et al. T-cell cytokines differentially control human monocyte antimicrobial responses by regulating vitamin D metabolism. Proc. Natl Acad. Sci. USA 107, 22593–22598 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Khoo, A.-L. et al. Vitamin D3 down-regulates proinflammatory cytokine response to Mycobacterium tuberculosis through pattern recognition receptors while inducing protective cathelicidin production. Cytokine 55, 294–300 (2011).

    Article  CAS  PubMed  Google Scholar 

  17. Baeke, F., Takiishi, T., Korf, H., Gysemans, C. & Mathieu, C. Vitamin D: modulator of the immune system. Curr. Opin. Pharmacol. 10, 482–496 (2010).

    Article  CAS  PubMed  Google Scholar 

  18. Penna, G. et al. 1,25-Dihydroxyvitamin D3 selectively modulates tolerogenic properties in myeloid but not plasmacytoid dendritic cells. J. Immunol. 178, 145–153 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. van der Aar, A. M. G. et al. Vitamin D3 targets epidermal and dermal dendritic cells for induction of distinct regulatory T cells. J. Allergy Clin. Immunol. 127, 1532–1540 (2011).

    Article  CAS  PubMed  Google Scholar 

  20. Baeke, F. et al. The vitamin D analog, TX527, promotes human CD4+CD25highCD127low regulatory T cell profile and induces a migratory signature specific for homing to sites of inflammation. J. Immunol. 186, 132–142 (2011).

    Article  CAS  PubMed  Google Scholar 

  21. Gibbs, N. K., Tye, J. & Norval, M. Recent advances in urocanic acid photochemistry, photobiology and photoimmunology. Photochem. Photobiol. Sci. 7, 655–667 (2008).

    Article  CAS  PubMed  Google Scholar 

  22. Halliday, G. M., Byrne, S. N., Kuchel, J. M., Poon, T. S. & Barnetson, R. S. The suppression of immunity by ultraviolet radiation: UVA, nitric oxide and DNA damage. Photochem. Photobiol. Sci. 3, 736–740 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Fritsche, E. et al. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmic target for ultraviolet B radiation. Proc. Natl Acad. Sci. USA 104, 8851–8856 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Hart, P. H., Townley, S. L., Grimbaldeston, M. A., Khalil, Z. & Finlay-Jones, J. J. Mast cells, neuropeptides, histamine and prostaglandins in UV-induced systemic immunosuppression. Methods 28, 79–89 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Ng, R. L. X., Bisley, J. L., Gorman, S., Norval, M. & Hart, P. H. UV-irradiation of mice reduces the competency of bone marrow-derived CD11c+ cells via an indomethacin-inhibitable pathway. J. Immunol. 185, 7207–7215 (2010).

    Article  CAS  PubMed  Google Scholar 

  26. Chacon-Salinas, R., Limon-Flores, A. Y., Chavez-Blanco, A. D., Gonzalez-Estrada, A. & Ullrich, S. E. Mast cell-derived IL-10 suppresses germinal center formation by affecting T follicular helper cell function. J. Immunol. 186, 25–31 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Veldhoen, M. & Duarte, J. H. The aryl hydrocarbon receptor: fine-tuning the immune response. Curr. Opin. Immunol. 22, 747–752 (2010).

    Article  CAS  PubMed  Google Scholar 

  28. Schwarz, T. 25 years of UV-induced immunosuppression mediated by T cells — from disregarded T suppressor cells to highly respected regulatory T cells. Photochem. Photobiol. 84, 10–18 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. Sreevidya, C. S. et al. Agents that reverse UV-induced immune suppression and photocarcinogenesis affect DNA repair. J. Invest. Dermatol. 130, 1428–1437 (2010).

    Article  CAS  PubMed  Google Scholar 

  30. Yiasemides, E., Sivapirabu, G., Halliday, G. M., Park, J. & Damian, D. L. Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis 30, 101–105 (2009).

    Article  CAS  PubMed  Google Scholar 

  31. Damian, D. L. et al. Topical calcitriol protects from UV-induced genetic damage but suppresses cutaneous immunity in humans. Exp. Dermatol. 19, e23–e30 (2010). The suppression of mantoux reactions in human skin by topical vitamin D was demonstrated. Vitamin D neither reduced nor enhanced UV-induced immunosuppression.

    Article  PubMed  Google Scholar 

  32. Gorman, S., Judge, M. A. & Hart, P. H. Immune-modifying properties of topical vitamin D: focus on dendritic cells and T cells. J. Steroid Biochem. Mol. Biol. 121, 247–249 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Schwarz, A. & Schwarz, T. UVR-induced regulatory T cells switch antigen-presenting cells from a stimulatory to a regulatory phenotype. J. Invest. Dermatol. 130, 1914–1921 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Barresi, C. et al. Increased sensitivity of histidinemic mice to UVB radiation suggests a crucial role of endogenous urocanic acid in photoprotection. J. Invest. Dermatol. 131, 188–194 (2011).

    Article  CAS  PubMed  Google Scholar 

  35. Kaneko, K. et al. cis-Urocanic acid initiates gene transcription in primary human keratinocytes. J. Immunol. 181, 217–224 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Albert, E., Walker, J., Thiesen, A., Churchill, T. & Madsen, K. cis-Urocanic acid attenuates acute dextran sodium sulphate-induced intestinal inflammation. PLoS ONE 5, e13676 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Bogh, M. K., Schmedes, A. V., Philipsen, P. A., Thieden, E. & Wulf, H. C. Vitamin D production after UVB exposure depends on baseline vitamin D and total cholesterol but not on skin pigmentation. J. Invest. Dermatol. 130, 546–553 (2010).

    Article  CAS  PubMed  Google Scholar 

  38. Lehmann, B., Sauter, W., Knuschke, P., Dressler, S. & Meurer, M. Demonstration of UVB-induced synthesis of 1α,25-dihydroxyvitamin D3 (calcitriol) in human skin by microdialysis. Arch. Dermatol. Res. 295, 24–28 (2003). This was the first study to measure the epidermal production of 1,25(OH) 2 D3 by UVB-irradiated human skin.

    Article  CAS  PubMed  Google Scholar 

  39. Bhan, I. et al. Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. J. Allergy Clin. Immunol. 127, 1302–1304 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Kreindler, J. L. et al. Vitamin D3 attenuates Th2 responses to Aspergillus fumigatus mounted by CD4+ T cells from cystic fibrosis patients with allergic bronchopulmonary aspergillosis. J. Clin. Invest. 120, 3242–3254 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hong, S. P. et al. Biopositive effects of low-dose UVB on epidermis: coordinate upregulation of antimicrobial peptides and permeability barrier reinforcement. J. Invest. Dermatol. 128, 2880–2887 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Biggs, L. et al. Evidence that vitamin D3 promotes mast cell-dependent reduction of chronic UVB-induced skin pathology in mice. J. Exp. Med. 207, 455–463 (2010). This study demonstrated that the effects of chronic UV on skin pathology in mice were due to UV-induced vitamin D3 on mast cell IL-10 production.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Ghoreishi, M. et al. Expansion of antigen-specific regulatory T cells with the topical vitamin D analog, calcipotriol. J. Immunol. 182, 6071–6078 (2009).

    Article  CAS  PubMed  Google Scholar 

  44. Gorman, S., Judge, M. A., Burchell, J. T., Turner, D. J. & Hart, P. H. 1,25-dihydroxyvitamin D3 enhances the ability of transferred CD4+ CD25+ cells to modulate T helper type 2-driven asthmatic responses. Immunology 130, 181–192 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Loser, K. et al. Epidermal RANKL controls regulatory T-cell numbers via activation of dendritic cells. Nature Med. 12, 1372–1379 (2006).

    Article  CAS  PubMed  Google Scholar 

  46. Hart, P. H. et al. Dermal mast cells determine susceptibility to ultraviolet B-induced systemic suppression of contact hypersensitivity responses in mice. J. Exp. Med. 187, 2045–2053 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Mason, R. S. et al. Photoprotection by 1α,25-dihydroxyvitamin D and analogs: further studies on mechanisms and implications for UV-damage. J. Steroid Biochem. Mol. Biol. 121, 164–168 (2010).

    Article  CAS  PubMed  Google Scholar 

  48. Enioutina, E. Y., Visic, D. M. & Daynes, R. A. The induction of systemic and mucosal immunity to protein vaccines delivered through skin sites exposed to UVB. Vaccine 20, 2116–2130 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Enioutina, E. Y., Bareyan, D. & Daynes, R. A. TLR-induced local metabolism of vitamin D3 plays an important role in the diversification of adaptive immune responses. J. Immunol. 182, 4296–4305 (2009).

    Article  CAS  PubMed  Google Scholar 

  50. Taher, Y. A., van Esch, B. C., Hofman, G. A., Henricks, P. A. J. & van Oosterhout, A. J. 1α,25-dihydroxyvitamin D3 potentiates the beneficial effects of allergen immunotherapy in a mouse model of allergic asthma: role for IL-10 and TGF-β. J. Immunol. 180, 5211–5221 (2008).

    Article  CAS  PubMed  Google Scholar 

  51. Bilu, D. & Sauder, D. N. Imiquimod: modes of action. Br. J. Dermatol. 149 (suppl. 66), 5–8 (2003).

    PubMed  Google Scholar 

  52. Stein, P. et al. UV exposure boosts transcutaneous immunization and improves tumor immunity: cytotoxic T-cell priming through the skin. J. Invest. Dermatol. 131, 211–219 (2011).

    Article  CAS  PubMed  Google Scholar 

  53. Sleijffers, A., Garssen, J. & Van Loveren, H. Ultraviolet radiation, resistance to infectious diseases, and vaccination responses. Methods 28, 111–121 (2002).

    Article  CAS  PubMed  Google Scholar 

  54. Sleijffers, A. et al. Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans. Photochem. Photobiol. 77, 271–275 (2003).

    Article  CAS  PubMed  Google Scholar 

  55. Plum, L. A. & DeLuca, H. F. Vitamin D, disease and therapeutic opportunities. Nature Rev. Drug Discov. 9, 941–955 (2010). This review comprehensively covers controversies associated with trials of supplementation with vitamin D or analogues for human diseases.

    Article  CAS  Google Scholar 

  56. Egan, K. M. Vitamin D and melanoma. Ann. Epidemiol. 19, 455–461 (2009).

    Article  PubMed  Google Scholar 

  57. Field, S. & Newton-Bishop, J. A. Melanoma and vitamin D. Mol. Oncol. 5, 197–214 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Gandini, S. et al. Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure. Eur. J. Cancer 41, 45–60 (2005).

    Article  PubMed  Google Scholar 

  59. Bikle, D. Nonclassic actions of vitamin D. J. Clin. Endocrinol. Metab. 94, 26–34 (2009).

    Article  CAS  PubMed  Google Scholar 

  60. Deeb, K. K., Trump, D. L. & Johnson, C. S. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Rev. Cancer 7, 684–700 (2007).

    Article  CAS  Google Scholar 

  61. Johnson-Huang, L. M. et al. Effective narrow-band UVB radiation therapy suppresses the IL-23/IL-17 axis in normalized psoriasis plaques. J. Invest. Dermatol. 130, 2654–2663 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Norval, M., Bjorn, L. O. & de Gruijl, F. R. Is the action spectrum for the UV-induced production of previtamin D3 in human skin correct? Photochem. Photobiol. Sci. 9, 11–17 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Hanneman, K. K., Scull, H. M., Cooper, K. D. & Baron, E. D. Effect of topical vitamin D analogue on in vivo contact sensitization. Arch. Dermatol. 142, 1332–1334 (2006).

    Article  PubMed  Google Scholar 

  64. van der Mei, I. A., Simpson, S., Stankovich, J. & Taylor, B. V. Individual and joint action of environmental factors and risk of MS. Neurol. Clin. 29, 233–255 (2011).

    Article  CAS  PubMed  Google Scholar 

  65. Staples, J., Ponsonby, A. L. & Lim, L. Low maternal exposure to ultraviolet radiation in pregnancy, month of birth, and risk of multiple sclerosis in offspring: longitudinal analysis. BMJ 340, c1640 (2010).

    PubMed  PubMed Central  Google Scholar 

  66. Munger, K. L. et al. Vitamin D intake and incidence of multiple sclerosis. Neurology 62, 60–65 (2004).

    Article  CAS  PubMed  Google Scholar 

  67. Munger, K. L., Levin, L. I., Hollis, B. W., Howard, N. S. & Ascherio, A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA 296, 2832–2838 (2006).

    Article  CAS  PubMed  Google Scholar 

  68. Smolders, J. et al. Vitamin D status is positively correlated with regulatory T cell function in patients with multiple sclerosis. PLoS ONE 13, e6635 (2009).

    Article  CAS  Google Scholar 

  69. Chang, J.-H., Cha, H.-R., Lee, D.-S., Seo, K. L. & Kweon, M.-N. 1,25-Dihydroxyvitamin D3 inhibits the differentiation and migration of TH17 cells to protect against experimental autoimmune encephalomyelitis. PLoS ONE 5, e12925 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Lucas, R. M. et al. Sun exposure and vitamin D are independent risk factors for CNS demyelination. Neurology 76, 540–548 (2011).

    Article  CAS  PubMed  Google Scholar 

  71. Becklund, B. R., Severson, K. S., Vang, S. V. & DeLuca, H. F. UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production. Proc. Natl Acad. Sci. USA 107, 6418–6423 (2010). This study concluded that UV radiation suppresses a mouse model of multiple sclerosis by processes independent of vitamin D, and that vitamin D supplementation may not replace the ability of sunlight to reduce susceptibility to multiple sclerosis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Mehta, B. K. New hypotheses on sunlight and the geographic variability of multiple sclerosis prevalence. J. Neurol. Sci. 192, 5–10 (2010).

    Article  Google Scholar 

  73. Gorman, S. et al. UV exposure and protection against allergic airways disease. Photochem. Photobiol. Sci. 9, 571–577 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Krstic, G. Asthma prevalence associated with geographical latitude and regional insolation in the United States of America and Australia. PLoS ONE 6, e18492 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dimeloe, S., Nanzer, A., Ryanna, K. & Hawrylowicz, C. Regulatory T cells, inflammation and the allergic response — the role of glucocorticoids and vitamin D. J. Steroid Biochem. Mol. Biol. 120, 86–95 (2010).

    Article  CAS  PubMed  Google Scholar 

  76. Hollams, E. M. et al. Vitamin D and atopy and asthma phenotypes in children: a longitudinal cohort study. Eur. Resp. J. 12 May 2011 (doi:10.1183/09031936.00029011).

    Article  CAS  PubMed  Google Scholar 

  77. Xystrakis, E. et al. Reversing the defective induction of IL-10-secreting regulatory T cells in glucocorticoid-resistant asthma patients. J. Clin. Invest. 116, 146–155 (2006). This was the first report of beneficial supplementation of steroid-resistant asthmatic patients with vitamin D. Vitamin D enhanced the responsiveness of their CD4+ T cells to dexamethasone and increased the production of regulatory IL-10.

    Article  CAS  PubMed  Google Scholar 

  78. Majak, P., Olszowiec-Chlebna, M., Smejda, K. & Stelmach, I. Vitamin D supplementation in children may prevent asthma exacerbation triggered by acute respiratory infection. J. Allergy Clin. Immunol. 127, 1294–1296 (2011).

    Article  PubMed  Google Scholar 

  79. Holt, P. G. & Sly, P. D. Interaction between adaptive and innate immune pathways in the pathogenesis of atopic asthma. Operation of a lung/bone marrow axis. Chest 139, 1165–1171 (2011).

    Article  PubMed  Google Scholar 

  80. Yu, C., Fedoric, B., Anderson, P. H., Lopez, A. F. & Grimbaldeston, M. A. Vitamin D3 signalling to mast cells: a new regulatory axis. Int. J. Biochem. Cell Biol. 43, 41–46 (2011).

    Article  CAS  PubMed  Google Scholar 

  81. Zosky, G. R. et al. Vitamin D deficiency causes deficits in lung function and alters lung structure. Am J. Respir. Crit. Care Med. 183, 1336–1343 (2011).

    Article  PubMed  Google Scholar 

  82. Martin, P. E. et al. Childhood eczema and rhinitis predict atopic but not nonatopic adult asthma: a prospective cohort study over 4 decades. J. Allergy Clin. Immunol. 127, 1473–1479 (2011).

    Article  PubMed  Google Scholar 

  83. Litonjua, A. A. & Weiss, S. T. Is vitamin D deficiency to blame for the asthma epidemic? J. Allergy Clin. Immunol. 120, 1031–1035 (2007).

    Article  CAS  PubMed  Google Scholar 

  84. Glaser, R. et al. UV-B radiation induces the expression of antimicrobial peptides in human keratinocytes in vitro and in vivo. J. Allergy Clin. Immunol. 123, 1117–1123 (2009).

    Article  PubMed  CAS  Google Scholar 

  85. Adams, J. S. et al. Vitamin D-directed rheostatic regulation of monocyte antibacterial responses. J. Immunol. 182, 4289–4295 (2009).

    Article  CAS  PubMed  Google Scholar 

  86. Norval, M. et al. The human health effects of ozone depletion and interactions with climate change. Photochem. Photobiol. Sci. 10, 199–225 (2011).

    Article  CAS  PubMed  Google Scholar 

  87. Bruce, D., Ooi, J. H., Yu, S. & Cantorna, M. T. Vitamin D and host resistance to infection? Putting the cart in front of the horse. Exp. Biol. Med. 235, 921–927 (2010).

    Article  CAS  Google Scholar 

  88. Yamshchikov, A. V., Desai, N. S., Blumberg, H. M., Ziegler, T. R. & Tangpricha, V. Vitamin D for treatment and prevention of infectious diseases: a systematic review of randomized controlled trials. Endocr. Pract. 15, 438–449 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  89. Martineau, A. R. et al. High-dose vitamin D3 during intensive-phase antimicrobial treatment of pulmonary tuberculosis: a double-blind randomized controlled trial. Lancet 377, 242–250 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Cantorna, M. T. Why do T cells express the vitamin D receptor? Ann. NY Acad. Sci. 1217, 77–82 (2011).

    Article  CAS  PubMed  Google Scholar 

  91. Weiss, S. T. Bacterial components plus vitamin D: the ultimate solution to the asthma (autoimmune disease) epidemic? J. Allergy Clin. Immunol. 127, 1128–1130 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Lagishetty, V. et al. Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis. Endocrinology 151, 2423–2432 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Urashima, M. et al. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in schoolchildren. Am. J. Clin. Nutr. 91, 1255–1260 (2010).

    Article  CAS  PubMed  Google Scholar 

  94. Garland, C. F., French, C. B., Baggerly, L. L. & Heaney, R. P. Vitamin D supplement doses and serum 25-hydroxyvitamin D in the range associated with cancer prevention. Anticancer Res. 31, 607–611 (2011).

    CAS  PubMed  Google Scholar 

  95. Ross, A. C. et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J. Clin. Endocrinol. Metab. 96, 53–58 (2011).

    Article  CAS  PubMed  Google Scholar 

  96. Roux, C. et al. New insights into the role of vitamin D and calcium in osteoporosis management: an expert roundtable discussion. Curr. Med. Res. Opin. 24, 1363–1370 (2008).

    Article  CAS  PubMed  Google Scholar 

  97. Rhodes, L. E. et al. Recommended summer sunlight exposure levels can produce sufficient (>20 ng/ml) but not the proposed optimal (>32 ng/ml) 25(OH)D levels at UK latitudes. J. Invest. Dermatol. 130, 1411–1418 (2010). Although controversial, this study highlights the difficulty of obtaining optimal vitamin D levels with recommended sunlight exposure in the UK, Europe and North America.

    Article  CAS  PubMed  Google Scholar 

  98. Webb, A. R., Kift, R., Berry, J. L. & Rhodes, L. E. The vitamin D debate: translating controlled experiments into reality for human sun exposure times. Photochem. Photobiol. 87, 741–745 (2011).

    Article  CAS  PubMed  Google Scholar 

  99. Wallace, A. M., Gibson, S., de la Hunty, A., Lamberg-Allardt, C. & Ashwell, M. Measurement of 25-hydroxyvitamin D in the clinical laboratory: current procedures, performance characteristics and limitations. Steroids 75, 477–488 (2010).

    Article  CAS  PubMed  Google Scholar 

  100. Hagenau, T. et al. Global vitamin D levels in relation to age, gender, skin pigmentation and latitude: an ecologic meta-regression analysis. Osteoporos. Int. 20, 133–140 (2009).

    Article  CAS  PubMed  Google Scholar 

  101. Kriegel, M. A., Manson, J. E. & Costenbader, K. H. Does vitamin D affect risk of developing autoimmune disease? A systematic review. Semin. Arthritis Rheum. 40, 512–531 (2011).

    Article  CAS  PubMed  Google Scholar 

  102. Yu, S. & Cantorna, M. T. Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J. Immunol. 186, 1384–1390 (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Dahl, M. V., McEwen, G. N. & Katz, H. I. Urocanic acid suppresses induction of immunity in human skin. Photoderm. Photoimmunol. Photomed. 26, 303–310 (2010).

    Article  CAS  Google Scholar 

  104. Kuchel, J. M., Barnetson, R. S. & Halliday, G. M. Cyclobutane pyrimidine dimer formation is a molecular trigger for solar-simulated ultraviolet radiation-induced suppression of memory immunity in humans. Photochem. Photobiol. Sci. 4, 577–582 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Camouse, M. M. et al. Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin. Exp. Dermatol. 18, 522–526 (2009).

    Article  PubMed  Google Scholar 

  106. Howes, R. A., Halliday, G. M., Barnetson, R. S., Friedmann, A. C. & Damian, D. L. Topical capsaicin reduces ultraviolet radiation-induced suppression of Mantoux reactions in humans. J. Dermatol. Sci. 44, 113–115 (2006).

    Article  CAS  PubMed  Google Scholar 

  107. Burton, J. M. et al. A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis. Neurology 74, 1852–1859 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gorman, S. et al. Vitamin D3 deficiency enhances allergen-induced lymphocyte responses in a mouse model of allergic airway disease. Pediatr. Allergy Immunol. (in the press).

  109. Mowry, E. M., James, J. A., Krupp, L. B. & Waubant, E. Vitamin D status and antibody levels to common viruses in pediatric-onset multiple sclerosis. Mult. Scler. 17, 666–671 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Norval, M. The effect of ultraviolet radiation on human viral infections. Photochem. Photobiol. 82, 1495–1504 (2006).

    Article  CAS  PubMed  Google Scholar 

  111. Cannell, J. J. et al. Epidemic influenza and vitamin D. Epidemiol. Infect. 134, 1129–1140 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors would like to thank M. Norval for valuable analysis of this Review and D. Damian for assistance with Table 1. Our research has been supported by the Australian National Health and Medical Research Council, the Cancer Council Western Australia, the Asthma Foundation of Western Australia, the Raine Foundation and the Brightspark Foundation.

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  1. Edith Cowan University, Perth, Western Australia, Australia.

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  1. Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, PO Box 855, Perth, 6872, Western Australia, Australia

    Prue H. Hart, Shelley Gorman & John J. Finlay-Jones

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Glossary

Suberythemal UV irradiation

An amount of UV irradiation that is not able to induce any detectable redness in the skin over a period of 24 hours after exposure.

Contact hypersensitivity response

A form of delayed-type hypersensitivity (type IV), in which T cells respond to antigens that are introduced through skin contact. This step requires dendritic cell mobilization from the skin to the draining lymph nodes to prime the antigen-specific T cells.

Photoadaptation

Reduced responses to a particular dose of UV radiation owing to the effects of prior multiple exposures of skin to UV radiation8.

Chromophores

Molecules that absorb selective wavelengths of light.

Nicotinamide adenine dinucleotide

(NAD). A coenzyme found in all living cells that exists in either an oxidized (NAD+) or a reduced (NADH) state. In metabolism, NAD is involved in redox reactions and carries electrons from one reaction to another. For example, NAD+ is required in the citric acid cycle for the production of ATP.

Thymine dimers

The predominant form of damage to DNA following UV radiation exposure, in which a covalent linkage is formed between two thymine bases. Thymine dimers alter DNA structure, inhibit polymerases, prevent accurate DNA replication and are mutagenic if not repaired.

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Hart, P., Gorman, S. & Finlay-Jones, J. Modulation of the immune system by UV radiation: more than just the effects of vitamin D?. Nat Rev Immunol 11, 584–596 (2011). https://doi.org/10.1038/nri3045

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