Photoimmunology: how ultraviolet radiation affects the immune system

Article metrics

Abstract

Ultraviolet (UV) radiation is a ubiquitous component of the environment that has important effects on a wide range of cell functions. Short-wavelength UVB radiation induces sunburn and is a potent immunomodulator, yet longer-wavelength, lower-energy UVA radiation also has effects on mammalian immunity. This Review discusses current knowledge regarding the mechanisms by which UV radiation can modify innate and adaptive immune responses and how this immunomodulatory capacity can be both beneficial in the case of inflammatory and autoimmune diseases, and detrimental in the case of skin cancer and the response to several infectious agents.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: UVR absorption by chromophores and damage recognition.
Fig. 2: Mechanisms of UVR-induced immunomodulation.
Fig. 3: The innate immune response is stimulated by the release of damage-associated molecular patterns following exposure to UVR.

References

  1. 1.

    Greene, M. I., Sy, M. S., Kripke, M. & Benacerraf, B. Impairment of antigen-presenting cell function by ultraviolet radiation. Proc. Natl Acad. Sci. USA 76, 6591–6595 (1979).

  2. 2.

    Schwarz, T., Urbanska, A., Gschnait, F. & Luger, T. A. Inhibition of the induction of contact hypersensitivity by a UV-mediated epidermal cytokine. J. Invest. Dermatol. 87, 289–291 (1986).

  3. 3.

    Breuer, J. et al. Ultraviolet B light attenuates the systemic immune response in central nervous system autoimmunity. Ann. Neurol. 75, 739–758 (2014).

  4. 4.

    Toews, G. B., Bergstresser, P. R. & Streilein, J. W. Epidermal Langerhans cell density determines whether contact hypersensitivity or unresponsiveness follows skin painting with DNFB. J. Immunol. 124, 445–453 (1980).

  5. 5.

    De Fabo, E. C. Arctic stratospheric ozone depletion and increased UVB radiation: potential impacts to human health. Int. J. Circumpolar Health 64, 509–522 (2005).

  6. 6.

    Halliday, G. M. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat. Res. 571, 107–120 (2005).

  7. 7.

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

  8. 8.

    Nghiem, D. X. et al. Ultraviolet a radiation suppresses an established immune response: implications for sunscreen design. J. Invest. Dermatol. 117, 1193–1199 (2001).

  9. 9.

    Moyal, D. D. & Fourtanier, A. M. Broad-spectrum sunscreens provide better protection from the suppression of the elicitation phase of delayed-type hypersensitivity response in humans. J. Invest. Dermatol. 117, 1186–1192 (2001).

  10. 10.

    Byrne, S. N., Spinks, N. & Halliday, G. M. Ultraviolet A irradiation of C57BL/6 mice suppresses systemic contact hypersensitivity or enhances secondary immunity depending on dose. J. Invest. Dermatol. 119, 858–864 (2002).

  11. 11.

    Kim, T. H., Ullrich, S. E., Ananthaswamy, H. N., Zimmerman, S. & Kripke, M. L. Suppression of delayed and contact hypersensitivity responses in mice have different UV dose responses. Photochem. Photobiol. 68, 738–744 (1998).

  12. 12.

    Matthews, Y. J., Halliday, G. M., Phan, T. A. & Damian, D. L. Wavelength dependency for UVA-induced suppression of recall immunity in humans. J. Dermatol. Sci. 59, 192–197 (2010).

  13. 13.

    Grether-Beck, S. et al. Activation of transcription factor AP-2 mediates UVA radiation- and singlet oxygen-induced expression of the human intercellular adhesion molecule 1 gene. Proc. Natl Acad. Sci. USA 93, 14586–14591 (1996).

  14. 14.

    Grether-Beck, S. et al. Non-enzymatic triggering of the ceramide signalling cascade by solar UVA radiation. EMBO J. 19, 5793–5800 (2000).

  15. 15.

    Polderman, M. C., Huizinga, T. W., Le Cessie, S. & Pavel, S. UVA-1 cold light treatment of SLE: a double blind, placebo controlled crossover trial. Ann. Rheum. Dis. 60, 112–115 (2001).

  16. 16.

    Noonan, F. P. & De Fabo, E. C. Immunosuppression by ultraviolet B radiation: initiation by urocanic acid. Immunol. Today 13, 250–254 (1992).

  17. 17.

    Gibbs, N. K. et al. Action spectra for the trans to cis photoisomerisation of urocanic acid in vitro and in mouse skin. Photochem. Photobiol. 57, 584–590 (1993).

  18. 18.

    Walterscheid, J. P. et al. Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression via the 5-HT2A receptor. Proc. Natl Acad. Sci. USA 103, 17420–17425 (2006). The first in vivo study to show that increased immunosuppression mediated by UVR exposure is associated with the metabolically stable analogue of platelet-activating factor (PAF) and dependent on the activation of the PAF receptor. This study also explores the possibility that oxidants are involved in the formation of PAF receptor ligands.

  19. 19.

    Kurimoto, I. & Streilein, J. W. cis-urocanic acid suppression of contact hypersensitivity induction is mediated via tumor necrosis factor-alpha. J. Immunol. 148, 3072–3078 (1992).

  20. 20.

    De Fabo, E. C. & Noonan, F. P. Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology. J. Exp. Med. 158, 84–98 (1983). The first demonstration that UV-irradiated mice are unable to reject UVR-induced tumours, which are highly antigenic and are thus rejected by normal syngeneic recipients.

  21. 21.

    Cumberbatch, M. & Kimber, I. Dermal tumour necrosis factor-alpha induces dendritic cell migration to draining lymph nodes, and possibly provides one stimulus for Langerhans’ cell migration. Immunology 75, 257–263 (1992).

  22. 22.

    Hart, P. H., Grimbaldeston, M. A., Swift, G. J., Hosszu, E. K. & Finlay-Jones, J. J. 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 (1999). This study shows that the anti-inflammatory cytokine IL-10 produced by mast cells limits the extent of lymphocyte infiltration during contact hypersensitivity.

  23. 23.

    Wille, J. J., Kydonieus, A. F. & Murphy, G. F. cis-urocanic acid induces mast cell degranulation and release of preformed TNF-alpha: a possible mechanism linking UVB and cis-urocanic acid to immunosuppression of contact hypersensitivity. Skin Pharmacol. Appl. Skin Physiol. 12, 18–27 (1999).

  24. 24.

    Prasad, R. & Katiyar, S. K. Prostaglandin E2 promotes UV radiation-induced immune suppression through DNA hypermethylation. Neoplasia 15, 795–804 (2013).

  25. 25.

    Ley, R. D. Photoreactivation of UV-induced pyrimidine dimers and erythema in the marsupial Monodelphis domestica. Proc. Natl Acad. Sci. USA 82, 2409–2411 (1985).

  26. 26.

    Kripke, M. L., Cox, P. A., Alas, L. G. & Yarosh, D. B. Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice. Proc. Natl Acad. Sci. USA 89, 7516–7520 (1992).

  27. 27.

    Yarosh, D. et al. Localization of liposomes containing a DNA repair enzyme in murine skin. J. Invest. Dermatol. 103, 461–468 (1994).

  28. 28.

    Stege, H. et al. Enzyme plus light therapy to repair DNA damage in ultraviolet-B-irradiated human skin. Proc. Natl Acad. Sci. USA 97, 1790–1795 (2000). The first demonstration that the generation of cyclobutane pyrimidine dimers in human skin has immunosuppressive effects.

  29. 29.

    Takebe, H., Nishigori, C. & Tatsumi, K. Melanoma and other skin cancers in xeroderma pigmentosum patients and mutation in their cells. J. Invest. Dermatol. 92, 236S–238S (1989).

  30. 30.

    Le May, N., Egly, J. M. & Coin, F. True lies: the double life of the nucleotide excision repair factors in transcription and DNA repair. J. Nucleic Acids 2010, 616342 (2010).

  31. 31.

    Petit-Frere, C. et al. Induction of interleukin-6 production by ultraviolet radiation in normal human epidermal keratinocytes and in a human keratinocyte cell line is mediated by DNA damage. J. Invest. Dermatol. 111, 354–359 (1998).

  32. 32.

    Schwarz, A. et al. Prevention of UV radiation-induced immunosuppression by IL-12 is dependent on DNA repair. J. Exp. Med. 201, 173–179 (2005).

  33. 33.

    Berneburg, M. et al. Singlet oxygen mediates the UVA-induced generation of the photoaging-associated mitochondrial common deletion. J. Biol. Chem. 274, 15345–15349 (1999).

  34. 34.

    Chen, A. C. et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N. Engl. J. Med. 373, 1618–1626 (2015).

  35. 35.

    Marathe, G. K. et al. Ultraviolet B radiation generates platelet-activating factor-like phospholipids underlying cutaneous damage. J. Biol. Chem. 280, 35448–35457 (2005).

  36. 36.

    Konger, R. L., Marathe, G. K., Yao, Y., Zhang, Q. & Travers, J. B. Oxidized glycerophosphocholines as biologically active mediators for ultraviolet radiation-mediated effects. Prostaglandins Other Lipid Mediat. 87, 1–8 (2008).

  37. 37.

    Alappatt, C., Johnson, C. A., Clay, K. L. & Travers, J. B. Acute keratinocyte damage stimulates platelet-activating factor production. Arch. Dermatol. Res. 292, 256–259 (2000).

  38. 38.

    Yao, Y. et al. Ultraviolet B radiation generated platelet-activating factor receptor agonist formation involves EGF-R-mediated reactive oxygen species. J. Immunol. 182, 2842–2848 (2009).

  39. 39.

    Calignano, A., Cirino, G., Meli, R. & Persico, P. Isolation and identification of platelet-activating factor in UV-irradiated guinea pig skin. J. Pharmacol. Methods 19, 89–91 (1988).

  40. 40.

    Shimizu, T. Lipid mediators in health and disease: enzymes and receptors as therapeutic targets for the regulation of immunity and inflammation. Annu. Rev. Pharmacol. Toxicol. 49, 123–150 (2009).

  41. 41.

    Walterscheid, J. P., Ullrich, S. E. & Nghiem, D. X. Platelet-activating factor, a molecular sensor for cellular damage, activates systemic immune suppression. J. Exp. Med. 195, 171–179 (2002).

  42. 42.

    Travers, J. B. et al. Identification of functional platelet-activating factor receptors on human keratinocytes. J. Invest. Dermatol. 105, 816–823 (1995).

  43. 43.

    Pei, Y. et al. Activation of the epidermal platelet-activating factor receptor results in cytokine and cyclooxygenase-2 biosynthesis. J. Immunol. 161, 1954–1961 (1998).

  44. 44.

    Chacon-Salinas, R. et al. An essential role for platelet-activating factor in activating mast cell migration following ultraviolet irradiation. J. Leukoc. Biol. 95, 139–148 (2014).

  45. 45.

    Esser, C. & Rannug, A. The aryl hydrocarbon receptor in barrier organ physiology, immunology, and toxicology. Pharmacol. Rev. 67, 259–279 (2015).

  46. 46.

    Funatake, C. J., Marshall, N. B., Steppan, L. B., Mourich, D. V. & Kerkvliet, N. I. Cutting edge: activation of the aryl hydrocarbon receptor by 2,3,7,8-tetrachlorodibenzo-p-dioxin generates a population of CD4+CD25+ cells with characteristics of regulatory T cells. J. Immunol. 175, 4184–4188 (2005).

  47. 47.

    Quintana, F. J. et al. An endogenous aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress experimental autoimmune encephalomyelitis. Proc. Natl Acad. Sci. USA 107, 20768–20773 (2010).

  48. 48.

    Hauben, E. et al. Activation of the aryl hydrocarbon receptor promotes allograft-specific tolerance through direct and dendritic cell-mediated effects on regulatory T cells. Blood 112, 1214–1222 (2008).

  49. 49.

    Stockinger, B., Di Meglio, P., Gialitakis, M. & Duarte, J. H. The aryl hydrocarbon receptor: multitasking in the immune system. Annu. Rev. Immunol. 32, 403–432 (2014).

  50. 50.

    Di Meglio, P. et al. Activation of the aryl hydrocarbon receptor dampens the severity of inflammatory skin conditions. Immunity 40, 989–1001 (2014).

  51. 51.

    Kadow, S. et al. Aryl hydrocarbon receptor is critical for homeostasis of invariant γδ T cells in the murine epidermis. J. Immunol. 187, 3104–3110 (2011).

  52. 52.

    Luecke, S. et al. The aryl hydrocarbon receptor (AHR), a novel regulator of human melanogenesis. Pigment Cell Melanoma Res. 23, 828–833 (2010).

  53. 53.

    Veldhoen, M. et al. The aryl hydrocarbon receptor links TH17-cell-mediated autoimmunity to environmental toxins. Nature 453, 106–109 (2008).

  54. 54.

    Kiss, E. A. et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334, 1561–1565 (2011).

  55. 55.

    Kawajiri, K. et al. Aryl hydrocarbon receptor suppresses intestinal carcinogenesis in Apc Min/+ mice with natural ligands. Proc. Natl Acad. Sci. USA 106, 13481–13486 (2009).

  56. 56.

    Gronke, K. et al. Interleukin-22 protects intestinal stem cells against genotoxic stress. Nature 566, 249–253 (2019).

  57. 57.

    Fritsche, E. et al. Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation. Proc. Natl Acad. Sci. USA 104, 8851–8856 (2007). The first demonstration that UVBR activates the aryl hydrocarbon receptor in keratinocytes through the generation of trytophan photoproducts and thereby elicits a gene response including expression of COX2.

  58. 58.

    Wei, Y. D., Rannug, U. & Rannug, A. UV-induced CYP1A1 gene expression in human cells is mediated by tryptophan. Chem. Biol. Interact. 118, 127–140 (1999).

  59. 59.

    Rannug, A. et al. Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances. J. Biol. Chem. 262, 15422–15427 (1987).

  60. 60.

    Schallreuter, K. U. et al. Blunted epidermal L-tryptophan metabolism in vitiligo affects immune response and ROS scavenging by Fenton chemistry, part 2: epidermal H2O2/ONOO--mediated stress in vitiligo hampers indoleamine 2,3-dioxygenase and aryl hydrocarbon receptor-mediated immune response signaling. FASEB J. 26, 2471–2485 (2012).

  61. 61.

    Wincent, E. et al. The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans. J. Biol. Chem. 284, 2690–2696 (2009).

  62. 62.

    Tigges, J. et al. The new aryl hydrocarbon receptor antagonist E/Z-2-benzylindene-5,6-dimethoxy-3,3-dimethylindan-1-one protects against UVB-induced signal transduction. J. Invest. Dermatol. 134, 556–559 (2014).

  63. 63.

    Navid, F. et al. The aryl hydrocarbon receptor is involved in UVR-induced immunosuppression. J. Invest. Dermatol. 133, 2763–2770 (2013).

  64. 64.

    Bruhs, A. et al. Activation of the arylhydrocarbon receptor causes immunosuppression primarily by modulating dendritic cells. J. Invest. Dermatol. 135, 435–444 (2015).

  65. 65.

    Rekik, R. et al. Impaired TGF-beta signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22. Cytokine 108, 182–189 (2018).

  66. 66.

    Tanaka, Y., Uchi, H., Hashimoto-Hachiya, A. & Furue, M. Tryptophan photoproduct FICZ upregulates IL1A, IL1B, and IL6 expression via oxidative stress in keratinocytes. Oxid. Med. Cell. Longev. 2018, 9298052 (2018).

  67. 67.

    Pollet, M. et al. The AHR represses nucleotide excision repair and apoptosis and contributes to UV-induced skin carcinogenesis. Cell Death Differ. 25, 1823–1836 (2018).

  68. 68.

    Holick, M. F. Vitamin D: a millenium perspective. J. Cell. Biochem. 88, 296–307 (2003).

  69. 69.

    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).

  70. 70.

    van der Aar, A. M. 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).

  71. 71.

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

  72. 72.

    Schwarz, A., Navid, F., Sparwasser, T., Clausen, B. E. & Schwarz, T. 1,25-dihydroxyvitamin D exerts similar immunosuppressive effects as UVR but is dispensable for local UVR-induced immunosuppression. J. Invest. Dermatol. 132, 2762–2769 (2012).

  73. 73.

    Matos, T. R. & Sheth, V. The symbiosis of phototherapy and photoimmunology. Clin. Dermatol. 34, 538–547 (2016).

  74. 74.

    Wang, T. T. et al. Cutting edge: 1,25-dihydroxyvitamin D3 is a direct inducer of antimicrobial peptide gene expression. J. Immunol. 173, 2909–2912 (2004).

  75. 75.

    Martin, E., Ganz, T. & Lehrer, R. I. Defensins and other endogenous peptide antibiotics of vertebrates. J. Leukoc. Biol. 58, 128–136 (1995).

  76. 76.

    Gallo, R. L. et al. Syndecans, cell surface heparan sulfate proteoglycans, are induced by a proline-rich antimicrobial peptide from wounds. Proc. Natl Acad. Sci. USA 91, 11035–11039 (1994).

  77. 77.

    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).

  78. 78.

    Bernard, J. J. & Gallo, R. L. Cyclooxygenase-2 enhances antimicrobial peptide expression and killing of Staphylococcus aureus. J. Immunol. 185, 6535–6544 (2010).

  79. 79.

    Chen, W., Tang, Q., Gonzales, M. S. & Bowden, G. T. Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes. Oncogene 20, 3921–3926 (2001).

  80. 80.

    Han, J. A. et al. p53-mediated induction of Cox-2 counteracts p53- or genotoxic stress-induced apoptosis. EMBO J. 21, 5635–5644 (2002).

  81. 81.

    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).

  82. 82.

    Mallbris, L., Edstrom, D. W., Sundblad, L., Granath, F. & Stahle, M. UVB upregulates the antimicrobial protein hCAP18 mRNA in human skin. J. Invest. Dermatol. 125, 1072–1074 (2005).

  83. 83.

    Heilborn, J. D., Weber, G., Gronberg, A., Dieterich, C. & Stahle, M. Topical treatment with the vitamin D analogue calcipotriol enhances the upregulation of the antimicrobial protein hCAP18/LL-37 during wounding in human skin in vivo. Exp. Dermatol. 19, 332–338 (2010).

  84. 84.

    Liu, P. T. et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 311, 1770–1773 (2006).

  85. 85.

    Bernard, J. J. et al. Ultraviolet radiation damages self noncoding RNA and is detected by TLR3. Nat. Med. 18, 1286–1290 (2012). This study shows that TLR3 in keratinocytes recognizes self-RNAs derived from UVR-damaged cells to elicit a sunburn response.

  86. 86.

    Gallo, R. L. & Bernard, J. J. Innate immune sensors stimulate inflammatory and immunosuppressive responses to UVB radiation. J. Invest. Dermatol. 134, 1508–1511 (2014).

  87. 87.

    Zhang, L. J. et al. Antimicrobial peptide LL37 and MAVS signaling drive interferon-β production by epidermal keratinocytes during skin injury. Immunity 45, 119–130 (2016).

  88. 88.

    Schwarz, T. & Luger, T. A. Effect of UV irradiation on epidermal cell cytokine production. J. Photochem. Photobiol. B. Biol. 4, 1–13 (1989).

  89. 89.

    Dombrowski, Y. et al. Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions. Sci. Transl Med. 3, 82ra38 (2011).

  90. 90.

    Sorensen, O. E. et al. Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors. J. Immunol. 170, 5583–5589 (2003).

  91. 91.

    Takahashi, T. et al. Cathelicidin promotes inflammation by enabling binding of self-RNA to cell surface scavenger receptors. Sci. Rep. 8, 4032 (2018).

  92. 92.

    Ahmad, I. et al. Toll-like receptor-4 deficiency enhances repair of UVR-induced cutaneous DNA damage by nucleotide excision repair mechanism. J. Invest. Dermatol. 134, 1710–1717 (2014).

  93. 93.

    Lewis, W. et al. Regulation of ultraviolet radiation induced cutaneous photoimmunosuppression by toll-like receptor-4. Arch. Biochem. Biophys. 508, 171–177 (2011). This study shows that TLR4 is required for UVR-induced immune suppression by showing that Tlr4 −/− mice, when compared with Tlr4 +/+ mice, are resistant to UVBR-induced immunosuppression.

  94. 94.

    Yoshikawa, T. & Streilein, J. W. Genetic basis of the effects of ultraviolet light B on cutaneous immunity. Evidence that polymorphism at the Tnfa and Lps loci governs susceptibility. Immunogenetics 32, 398–405 (1990).

  95. 95.

    Miller, Y. I. & Shyy, J. Y. Context-dependent role of oxidized lipids and lipoproteins in inflammation. Trends Endocrinol. Metab. 28, 143–152 (2017).

  96. 96.

    Trautinger, F., Kindas-Mugge, I., Knobler, R. M. & Honigsmann, H. Stress proteins in the cellular response to ultraviolet radiation. J. Photochem. Photobiol. B. Biol. 35, 141–148 (1996).

  97. 97.

    Klune, J. R., Dhupar, R., Cardinal, J., Billiar, T. R. & Tsung, A. HMGB1: endogenous danger signaling. Mol. Med. 14, 476–484 (2008).

  98. 98.

    Gariboldi, S. et al. Low molecular weight hyaluronic acid increases the self-defense of skin epithelium by induction of β-defensin 2 via TLR2 and TLR4. J. Immunol. 181, 2103–2110 (2008).

  99. 99.

    Nakatsuji, T. et al. The microbiome extends to subepidermal compartments of normal skin. Nat. Commun. 4, 1431 (2013).

  100. 100.

    Lande, R. et al. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 449, 564–569 (2007).

  101. 101.

    Chamilos, G. et al. Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37. Blood 120, 3699–3707 (2012).

  102. 102.

    Schwarz, T. & Beissert, S. Milestones in photoimmunology. J. Invest. Dermatol. 133, E7–E10 (2013).

  103. 103.

    Damiani, E. & Ullrich, S. E. Understanding the connection between platelet-activating factor, a UV-induced lipid mediator of inflammation, immune suppression and skin cancer. Prog. Lipid Res. 63, 14–27 (2016).

  104. 104.

    Vieyra-Garcia, P. A. & Wolf, P. From early immunomodulatory triggers to immunosuppressive outcome: therapeutic implications of the complex interplay between the wavebands of sunlight and the skin. Front. Med. 5, 232 (2018).

  105. 105.

    Hart, P. H., Norval, M., Byrne, S. N. & Rhodes, L. E. Exposure to ultraviolet radiation in the modulation of human diseases. Annu. Rev. Pathol. 14, 55–81 (2019).

  106. 106.

    Elmets, C. A., Cala, C. M. & Xu, H. Photoimmunology. Dermatol. Clin. 32, 277–290 (2014).

  107. 107.

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

  108. 108.

    Fisher, M. S. & Kripke, M. L. Suppressor T lymphocytes control the development of primary skin cancers in ultraviolet-irradiated mice. Science 216, 1133–1134 (1982).

  109. 109.

    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).

  110. 110.

    Streilein, J. W., Toews, G. T., Gilliam, J. N. & Bergstresser, P. R. Tolerance or hypersensitivity to 2,4-dinitro-1-fluorobenzene: the role of Langerhans cell density within epidermis. J. Invest. Dermatol. 74, 319–322 (1980).

  111. 111.

    Elmets, C. A., Bergstresser, P. R., Tigelaar, R. E., Wood, P. J. & Streilein, J. W. Analysis of the mechanism of unresponsiveness produced by haptens painted on skin exposed to low dose ultraviolet radiation. J. Exp. Med. 158, 781–794 (1983).

  112. 112.

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

  113. 113.

    Yamazaki, S. et al. CD8+CD205+ splenic dendritic cells are specialized to induce Foxp3+ regulatory T cells. J. Immunol. 181, 6923–6933 (2008).

  114. 114.

    Soontrapa, K. et al. Prostaglandin E2-prostaglandin E receptor subtype 4 (EP4) signaling mediates UV irradiation-induced systemic immunosuppression. Proc. Natl Acad. Sci. USA 108, 6668–6673 (2011).

  115. 115.

    Reeve, V. E., Matheson, M. J., Bosnic, M. & Boehm-Wilcox, C. The protective effect of indomethacin on photocarcinogenesis in hairless mice. Cancer Lett. 95, 213–219 (1995).

  116. 116.

    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).

  117. 117.

    Byrne, S. N., Beaugie, C., O’Sullivan, C., Leighton, S. & Halliday, G. M. The immune-modulating cytokine and endogenous Alarmin interleukin-33 is upregulated in skin exposed to inflammatory UVB radiation. Am. J. Pathol. 179, 211–222 (2011).

  118. 118.

    Alard, P., Kurimoto, I., Niizeki, H., Doherty, J. M. & Streilein, J. W. Hapten-specific tolerance induced by acute, low-dose ultraviolet B radiation of skin requires mast cell degranulation. Eur. J. Immunol. 31, 1736–1746 (2001).

  119. 119.

    Galli, S. J., Grimbaldeston, M. & Tsai, M. Immunomodulatory mast cells: negative, as well as positive, regulators of immunity. Nat. Rev. Immunol. 8, 478–486 (2008).

  120. 120.

    Matheson, M. J. & Reeve, V. E. The effect of the antihistamine cimetidine on ultraviolet-radiation-induced tumorigenesis in the hairless mouse. Photochem. Photobiol. 53, 639–642 (1991).

  121. 121.

    Griswold, D. E., Alessi, S., Badger, A. M., Poste, G. & Hanna, N. Inhibition of T suppressor cell expression by histamine type 2 (H2) receptor antagonists. J. Immunol. 132, 3054–3057 (1984).

  122. 122.

    Jaksic, A. et al. Cis-urocanic acid synergizes with histamine for increased PGE2 production by human keratinocytes: link to indomethacin-inhibitable UVB-induced immunosuppression. Photochem. Photobiol. 61, 303–309 (1995).

  123. 123.

    Laberge, S., Cruikshank, W. W., Kornfeld, H. & Center, D. M. Histamine-induced secretion of lymphocyte chemoattractant factor from CD8+ T cells is independent of transcription and translation. Evidence for constitutive protein synthesis and storage. J. Immunol. 155, 2902–2910 (1995).

  124. 124.

    Lagier, B., Lebel, B., Bousquet, J. & Pene, J. Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones. Clin. Exp. Immunol. 108, 545–551 (1997).

  125. 125.

    Elenkov, I. J. et al. Histamine potently suppresses human IL-12 and stimulates IL-10 production via H2 receptors. J. Immunol. 161, 2586–2593 (1998).

  126. 126.

    Grimbaldeston, M. A., Nakae, S., Kalesnikoff, J., Tsai, M. & Galli, S. J. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nat. Immunol. 8, 1095–1104 (2007).

  127. 127.

    Rana, S., Byrne, S. N., MacDonald, L. J., Chan, C. Y. & Halliday, G. M. Ultraviolet B suppresses immunity by inhibiting effector and memory T cells. Am. J. Pathol. 172, 993–1004 (2008).

  128. 128.

    Shreedhar, V. K., Pride, M. W., Sun, Y., Kripke, M. L. & Strickland, F. M. Origin and characteristics of ultraviolet-B radiation-induced suppressor T lymphocytes. J. Immunol. 161, 1327–1335 (1998).

  129. 129.

    Moodycliffe, A. M., Nghiem, D., Clydesdale, G. & Ullrich, S. E. Immune suppression and skin cancer development: regulation by NKT cells. Nat. Immunol. 1, 521–525 (2000).

  130. 130.

    Fukunaga, A. et al. Langerhans cells serve as immunoregulatory cells by activating NKT cells. J. Immunol. 185, 4633–4640 (2010).

  131. 131.

    Byrne, S. N. & Halliday, G. M. B cells activated in lymph nodes in response to ultraviolet irradiation or by interleukin-10 inhibit dendritic cell induction of immunity. J. Invest. Dermatol. 124, 570–578 (2005).

  132. 132.

    Matsumura, Y., Byrne, S. N., Nghiem, D. X., Miyahara, Y. & Ullrich, S. E. A role for inflammatory mediators in the induction of immunoregulatory B cells. J. Immunol. 177, 4810–4817 (2006).

  133. 133.

    Mizoguchi, A., Mizoguchi, E., Takedatsu, H., Blumberg, R. S. & Bhan, A. K. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 16, 219–230 (2002).

  134. 134.

    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).

  135. 135.

    Hawk, J. L., Murphy, G. M. & Holden, C. A. The presence of neutrophils in human cutaneous ultraviolet-B inflammation. Br. J. Dermatol. 118, 27–30 (1988).

  136. 136.

    Teunissen, M. B. et al. Ultraviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses. J. Immunol. 168, 3732–3739 (2002).

  137. 137.

    Piskin, G., Bos, J. D. & Teunissen, M. B. Neutrophils infiltrating ultraviolet B-irradiated normal human skin display high IL-10 expression. Arch. Dermatol. Res. 296, 339–342 (2005).

  138. 138.

    Love, L. A. et al. Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women. Arthritis Rheum. 60, 2499–2504 (2009).

  139. 139.

    Artukovic, M., Ikic, M., Kustelega, J., Artukovic, I. N. & Kaliterna, D. M. Influence of UV radiation on immunological system and occurrence of autoimmune diseases. Coll. Antropol. 34 (Suppl. 2), 175–178 (2010).

  140. 140.

    Barbhaiya, M. & Costenbader, K. H. Ultraviolet radiation and systemic lupus erythematosus. Lupus 23, 588–595 (2014).

  141. 141.

    Baer, R. L. & Harber, L. C. Photobiology of lupus erythematosus. Arch. Dermatol. 92, 124–128 (1965).

  142. 142.

    Kemp, M. G., Lindsey-Boltz, L. A. & Sancar, A. UV light potentiates STING (stimulator of interferon genes)-dependent innate immune signaling through deregulation of ULK1 (Unc51-like kinase 1). J. Biol. Chem. 290, 12184–12194 (2015).

  143. 143.

    Cai, X., Chiu, Y. H. & Chen, Z. J. The cGAS-cGAMP-STING pathway of cytosolic DNA sensing and signaling. Mol. Cell 54, 289–296 (2014).

  144. 144.

    O’Neill, L. A. Sensing the dark side of DNA. Science 339, 763–764 (2013).

  145. 145.

    Ishikawa, H. & Barber, G. N. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature 455, 674–678 (2008).

  146. 146.

    Birner, P. et al. Interleukin-6 receptor alpha blockade improves skin lesions in a murine model of systemic lupus erythematosus. Exp. Dermatol. 25, 305–310 (2016).

  147. 147.

    McGrath, H. Jr. Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus. Lupus 26, 1239–1251 (2017).

  148. 148.

    Szegedi, A. et al. Ultraviolet-A1 phototherapy modulates Th1/Th2 and Tc1/Tc2 balance in patients with systemic lupus erythematosus. Rheumatology 44, 925–931 (2005).

  149. 149.

    Wolf, P., Weger, W., Patra, V., Gruber-Wackernagel, A. & Byrne, S. N. Desired response to phototherapy versus photoaggravation in psoriasis: what makes the difference? Exp. Dermatol. 25, 937–944 (2016).

  150. 150.

    Enk, C. D., Sredni, D., Blauvelt, A. & Katz, S. I. Induction of IL-10 gene expression in human keratinocytes by UVB exposure in vivo and in vitro. J. Immunol. 154, 4851–4856 (1995).

  151. 151.

    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).

  152. 152.

    Furuhashi, T. et al. Photo(chemo)therapy reduces circulating Th17 cells and restores circulating regulatory T cells in psoriasis. PLOS ONE 8, e54895 (2013).

  153. 153.

    DeSilva, B., McKenzie, R. C., Hunter, J. A. & Norval, M. Local effects of TL01 phototherapy in psoriasis. Photodermatol. Photoimmunol. Photomed. 24, 268–269 (2008).

  154. 154.

    McLoone, P., Woods, G. M. & Norval, M. Decrease in Langerhans cells and increase in lymph node dendritic cells following chronic exposure of mice to suberythemal doses of solar simulated radiation. Photochem. Photobiol. 81, 1168–1173 (2005).

  155. 155.

    Racz, E. et al. Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes. Br. J. Dermatol. 164, 838–847 (2011).

  156. 156.

    Walder, B. K., Robertson, M. R. & Jeremy, D. Skin cancer and immunosuppression. Lancet 2, 1282–1283 (1971).

  157. 157.

    Hardie, I. R., Strong, R. W., Hartley, L. C., Woodruff, P. W. & Clunie, G. J. Skin cancer in Caucasian renal allograft recipients living in a subtropical climate. Surgery 87, 177–183 (1980).

  158. 158.

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

  159. 159.

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

  160. 160.

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

  161. 161.

    Stein, B. et al. Ultraviolet-radiation induced c-Jun gene transcription: two AP-1 like binding sites mediate the response. Photochem. Photobiol. 55, 409–415 (1992).

  162. 162.

    Loiacono, C. M., Taus, N. S. & Mitchell, W. J. The herpes simplex virus type 1 ICP0 promoter is activated by viral reactivation stimuli in trigeminal ganglia neurons of transgenic mice. J. Neurovirol. 9, 336–345 (2003).

  163. 163.

    Zak-Prelich, M., Borkowski, J. L., Alexander, F. & Norval, M. The role of solar ultraviolet irradiation in zoster. Epidemiol. Infect. 129, 593–597 (2002).

  164. 164.

    Korostil, I. A. & Regan, D. G. Varicella-zoster virus in Perth, Western Australia: seasonality and reactivation. PLOS ONE 11, e0151319 (2016).

  165. 165.

    Cahoon, E. K., Engels, E. A., Freedman, D. M., Norval, M. & Pfeiffer, R. M. Ultraviolet radiation and Kaposi sarcoma incidence in a nationwide US cohort of HIV-infected men. J. Natl Cancer Inst. 109, djw267 (2017).

  166. 166.

    Pacini, L. et al. UV radiation activates Toll-like receptor 9 expression in primary human keratinocytes, an event inhibited by human papillomavirus 38 E6 and E7 oncoproteins. J. Virol. 91, e01123–17 (2017).

  167. 167.

    Liu, W. et al. Identifying the target cells and mechanisms of Merkel cell polyomavirus infection. Cell Host Microbe 19, 775–787 (2016).

  168. 168.

    Chen, Q. et al. Prevention of ultraviolet radiation-induced immunosuppression by sunscreen in Candida albicans-induced delayed-type hypersensitivity. Mol. Med. Rep. 14, 202–208 (2016).

  169. 169.

    Brown, E. L., Ullrich, S. E., Pride, M. & Kripke, M. L. The effect of UV irradiation on infection of mice with Borrelia burgdorferi. Photochem. Photobiol. 73, 537–544 (2001).

  170. 170.

    Garssen, J. et al. A rat cytomegalovirus infection model as a tool for immunotoxicity testing. Eur. J. Pharmacol. 292, 223–231 (1995).

  171. 171.

    Ryan, L. K. et al. Exposure to ultraviolet radiation enhances mortality and pathology associated with influenza virus infection in mice. Photochem. Photobiol. 72, 497–507 (2000).

  172. 172.

    Boere, T. M., Visser, D. H., van Furth, A. M., Lips, P. & Cobelens, F. G. J. Solar ultraviolet B exposure and global variation in tuberculosis incidence: an ecological analysis. Eur. Respir. J. 49, 1601979 (2017).

  173. 173.

    Norval, M. & Halliday, G. M. The consequences of UV-induced immunosuppression for human health. Photochem. Photobiol. 87, 965–977 (2011).

  174. 174.

    John, T. J. & Christopher, S. Oral polio vaccination of children in the tropics. III. Intercurrent enterovirus infections, vaccine virus take and antibody response. Am. J. Epidemiol. 102, 422–428 (1975).

  175. 175.

    Swartz, T. A., Skalska, P., Gerichter, C. G. & Cockburn, W. C. Routine administration of oral polio vaccine in a subtropical area. Factors possibly influencing sero-conversion rates. J. Hyg. 70, 719–726 (1972).

  176. 176.

    Zykov, M. P. & Sosunov, A. V. Vaccination activity of live influenza vaccine in different seasons of the year. J. Hyg. Epidemiol. Microbiol. Immunol. 31, 453–459 (1987).

  177. 177.

    Linder, N. et al. Effect of season of inoculation on immune response to rubella vaccine in children. J. Trop. Pediatr. 57, 299–302 (2011).

  178. 178.

    Sleijffers, A. et al. Influence of ultraviolet B exposure on immune responses following hepatitis B vaccination in human volunteers. J. Invest. Dermatol. 117, 1144–1150 (2001).

  179. 179.

    Sleijffers, A. et al. Cytokine polymorphisms play a role in susceptibility to ultraviolet B-induced modulation of immune responses after hepatitis B vaccination. J. Immunol. 170, 3423–3428 (2003).

  180. 180.

    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).

  181. 181.

    Cela, E. M. et al. Time-course study of different innate immune mediators produced by UV-irradiated skin: comparative effects of short and daily versus a single harmful UV exposure. Immunology 145, 82–93 (2015).

  182. 182.

    Khaskhely, N. M. et al. Low-dose UVB contributes to host resistance against Leishmania amazonensis infection in mice through induction of gamma interferon and tumor necrosis factor alpha cytokines. Clin. Diagn. Lab. Immunol. 9, 677–686 (2002).

  183. 183.

    Krutmann, J., Morita, A. & Chung, J. H. Sun exposure: what molecular photodermatology tells us about its good and bad sides. J. Invest. Dermatol. 132, 976–984 (2012).

  184. 184.

    Danno, K. & Sugie, N. Effects of near-infrared radiation on the epidermal proliferation and cutaneous immune function in mice. Photodermatol. Photoimmunol. Photomed. 12, 233–236 (1996).

  185. 185.

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

  186. 186.

    Salmon, J. K., Armstrong, C. A. & Ansel, J. C. The skin as an immune organ. West. J. Med. 160, 146–152 (1994).

  187. 187.

    Damian, D. L. et al. UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. J. Invest. Dermatol. 128, 447–454 (2008).

  188. 188.

    Reeve, V. E., Allanson, M., Domanski, D. & Painter, N. Gender differences in UV-induced inflammation and immunosuppression in mice reveal male unresponsiveness to UVA radiation. Photochem. Photobiol. Sci. 11, 173–179 (2012).

  189. 189.

    Thomas-Ahner, J. M. et al. Gender differences in UVB-induced skin carcinogenesis, inflammation, and DNA damage. Cancer Res. 67, 3468–3474 (2007).

  190. 190.

    Ansar Ahmed, S., Penhale, W. J. & Talal, N. Sex hormones, immune responses, and autoimmune diseases. Mechanisms of sex hormone action. Am. J. Pathol. 121, 531–551 (1985).

  191. 191.

    Noonan, F. P. & Hoffman, H. A. Susceptibility to immunosuppression by ultraviolet B radiation in the mouse. Immunogenetics 39, 29–39 (1994).

  192. 192.

    Yoshikawa, T. et al. Susceptibility to effects of UVB radiation on induction of contact hypersensitivity as a risk factor for skin cancer in humans. J. Invest. Dermatol. 95, 530–536 (1990). The first study to show that failure to induce contact hypersensitivity at UVR-exposed sites is associated with a higher risk of skin cancer in humans.

  193. 193.

    Alamartine, E., Berthoux, P., Mariat, C., Cambazard, F. & Berthoux, F. Interleukin-10 promoter polymorphisms and susceptibility to skin squamous cell carcinoma after renal transplantation. J. Invest. Dermatol. 120, 99–103 (2003).

  194. 194.

    Nagano, T., Kunisada, M., Yu, X., Masaki, T. & Nishigori, C. Involvement of interleukin-10 promoter polymorphisms in nonmelanoma skin cancers-a case study in non-Caucasian skin cancer patients. Photochem. Photobiol. 84, 63–66 (2008).

  195. 195.

    Chahal, H. S. et al. Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma. Nat. Commun. 7, 12048 (2016).

  196. 196.

    Sharma, M. R., Werth, B. & Werth, V. P. Animal models of acute photodamage: comparisons of anatomic, cellular and molecular responses in C57BL/6J, SKH1 and Balb/c mice. Photochem. Photobiol. 87, 690–698 (2011).

  197. 197.

    Gombart, A. F., Borregaard, N. & Koeffler, H. P. Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target of the vitamin D receptor and is strongly up-regulated in myeloid cells by 1,25-dihydroxyvitamin D3. FASEB J. 19, 1067–1077 (2005).

  198. 198.

    Berthier-Vergnes, O. et al. TNF-α enhances phenotypic and functional maturation of human epidermal Langerhans cells and induces IL-12 p40 and IP-10/CXCL-10 production. FEBS Lett. 579, 3660–3668 (2005).

  199. 199.

    Grewe, M., Gyufko, K. & Krutmann, J. Interleukin-10 production by cultured human keratinocytes: regulation by ultraviolet B and ultraviolet A1 radiation. J. Invest. Dermatol. 104, 3–6 (1995).

Download references

Acknowledgements

The authors acknowledge research support by grants from Michigan State University Gran Fondo funds, NIH R00 CA177868, the German Federal Ministry for Education and Research (BMBF: 02NUK036C/KAUVIR), NIH R01AI052453 and NIH R01AR069653. The authors thank W. Shoemaker (Michigan State University), T. Haarmann-Stemmann (IUF) and C. Esser (IUF) for their help with manuscript preparation.

Author information

All authors contributed to researching content for the manuscript, writing the manuscript and editing before submission.

Correspondence to Jamie J. Bernard.

Ethics declarations

Competing interests

R.L.G. is a consultant for and has equity interest in MatriSys BioScience and Sente Inc. The other authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Peer review information

Nature Reviews Immunology thanks P. Hart, T. Schwarz and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

Glossary

Contact hypersensitivity

(CHS). A T cell-mediated and antigen-specific inflammatory response in which the exposure of epidermal cells to exogenous haptens results in a delayed-type hypersensitivity reaction that can be experimentally measured and quantified.

Chromophores

The parts of a photoreceptor that absorb photons of light, using a mechanism that involves a change in configuration.

Melanogenesis

The production of melanin pigments by melanocytes in the basal layer of the epidermis.

Porphyrins

A group of heterocyclic macrocycle organic compounds composed of four modified pyrrole subunits interconnected at their α-carbon atoms by methine bridges.

Singlet oxygen

The reactive oxygen species 1O2.

Urocanic acid

(UCA). A breakdown (deamination) product of histidine that is an important epidermal chromophore for ultraviolet radiation.

Nucleotide excision repair

(NER). A mechanism to remove DNA damage, such as the thymine dimers and 6,4-photoproducts that are induced by ultraviolet radiation.

Xeroderma pigmentosum

An autosomal recessive genetic disorder that causes cellular hypersensitivity to ultraviolet radiation as a result of a defect in the DNA repair system.

Reactive oxygen intermediates

(ROIs). Successive one-electron reduction products of O2, including superoxide anions, hydrogen peroxide and hydroxyl radicals; ROIs are chemically reactive with unpaired electrons.

Minimal erythemal dose

The threshold dose of ultraviolet radiation that can produce sunburn.

Dermatomyositis

An uncommon inflammatory myopathy characterized by degenerative changes to the muscles and skin.

Dinitrochlorobenzene

1-Chloro-2,4-dinitrobenzene is an organic, potent contact allergen.

Psoralen plus UVA

A therapy for skin conditions, including psoriasis, eczema and vitiligo, that is composed of a plant-derived ultraviolet (UV)-sensitizer compound (psoralen), combined with UVA radiation (long wavelength radiation).

Impetigo

A common and highly contagious skin infection that mainly affects infants and children; it usually occurs as red sores on the face.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark