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Multifaceted pathways protect human skin from UV radiation

Nature Chemical Biology volume 10, pages 542–551 (2014)Cite this article

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Abstract

The recurrent interaction of skin with sunlight is an intrinsic constituent of human life, and exhibits both beneficial and detrimental effects. The apparent robust architectural framework of skin conceals remarkable mechanisms that operate at the interface between the surface and environment. In this Review, we discuss three distinct protective mechanisms and response pathways that safeguard skin from deleterious effects of ultraviolet (UV) radiation. The unique stratified epithelial architecture of human skin along with the antioxidant-response pathways constitutes the important defense mechanisms against UV radiation. The intricate pigmentary system and its intersection with the immune-system cytokine axis delicately balance tissue homeostasis. We discuss the relationship among these networks in the context of an unusual depigmenting disorder, vitiligo. The elaborate tunable mechanisms, elegant multilayered architecture and evolutionary selection pressures involved in skin and sunlight interaction makes this a compelling model to understand biological complexity.

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Figure 1: Architecture of epidermal cell layers of human skin.
Figure 2: Schematic of skin lipids and their associated pathway in epidermal layers.
Figure 3: Photodamage and stress response in the skin.
Figure 4: Kinetics of pigmentation response and pathways activated in the epidermis upon exposure to UV light.
Figure 5: Temporal regulation of skin pigmentation by IFN-γ: scheme of events in melanocytes and keratinocytes as a part of a delayed tanning response and recovery.
Figure 6: Photograph of an individual with vitiligo.

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References

  1. Dyck, J. Structure and colour-production of the blue barbs of Agapornis roseicollis and Cotinga maynana. Z. Zellforsch. Mikrosk. Anat. 115, 17–29 (1971).

    CAS  PubMed  Google Scholar 

  2. Pathak, M.A., Riley, F.J., Fitzpatrick, T.B. & Curwen, W.L. Melanin formation in human skin induced by long-wave ultra-violet and visible light. Nature 193, 148–150 (1962).

    CAS  PubMed  Google Scholar 

  3. 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).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  5. Janich, P. et al. Human epidermal stem cell function is regulated by circadian oscillations. Cell Stem Cell 13, 745–753 (2013).

    CAS  PubMed  Google Scholar 

  6. Bowden, G.T. Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling. Nat. Rev. Cancer 4, 23–35 (2004).

    CAS  PubMed  Google Scholar 

  7. Rigel, D.S. Cutaneous ultraviolet exposure and its relationship to the development of skin cancer. J. Am. Acad. Dermatol. 58, S129–S132 (2008).

    PubMed  Google Scholar 

  8. Bald, T. et al. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507, 109–113 (2014). Ancillary role of sunlight in facilitating metastasis of melanoma by the induction of angiotropic factor HMGB1 is deciphered and this study provides molecular explanation of sun exposure induced melanoma spread.

    CAS  PubMed  Google Scholar 

  9. Wondrak, G.T., Jacobson, M.K. & Jacobson, E.L. Endogenous UVA-photosensitizers: mediators of skin photodamage and novel targets for skin photoprotection. Photochem. Photobiol. Sci. 5, 215–237 (2006).

    CAS  PubMed  Google Scholar 

  10. Dalle Carbonare, M. & Pathak, M.A. Skin photosensitizing agents and the role of reactive oxygen species in photoaging. J. Photochem. Photobiol. B 14, 105–124 (1992).

    CAS  PubMed  Google Scholar 

  11. Lechler, T. & Fuchs, E. Asymmetric cell divisions promote stratification and differentiation of mammalian skin. Nature 437, 275–280 (2005). Niche-dependent oriented cell divisions in the basal epidermal layer are described, and the crucial role of intercellular connections in the control of asymmetric cell divisions is highlighted.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lin, J.Y. & Fisher, D.E. Melanocyte biology and skin pigmentation. Nature 445, 843–850 (2007).

    CAS  PubMed  Google Scholar 

  13. Yamaguchi, Y., Brenner, M. & Hearing, V.J. The regulation of skin pigmentation. J. Biol. Chem. 282, 27557–27561 (2007). This is an excellent compilation of regulatory pathways that govern pigmentation during developmental and constitutive pigmentation in human epidermis.

    CAS  PubMed  Google Scholar 

  14. Miyamura, Y. et al. Regulation of human skin pigmentation and responses to ultraviolet radiation. Pigment Cell Res. 20, 2–13 (2007).

    CAS  PubMed  Google Scholar 

  15. Rawlings, A.V. & Harding, C.R. Moisturization and skin barrier function. Dermatol. Ther. 17 (suppl. 1): 43–48 (2004).

    PubMed  Google Scholar 

  16. Wertz, P.W. Current understanding of skin biology pertinent to skin penetration: skin biochemistry. Skin Pharmacol. Physiol. 26, 217–226 (2013).

    CAS  PubMed  Google Scholar 

  17. Del Rosso, J.Q. & Levin, J. Clinical relevance of maintaining the structural and functional integrity of the stratum corneum: why is it important to you? J. Drugs Dermatol. 10, s5–s12 (2011).

    PubMed  Google Scholar 

  18. Koster, M.I. & Roop, D.R. Mechanisms regulating epithelial stratification. Annu. Rev. Cell Dev. Biol. 23, 93–113 (2007).

    CAS  PubMed  Google Scholar 

  19. Elias, P.M. et al. Formation and functions of the corneocyte lipid envelope (CLE). Biochim. Biophys. Acta 1841, 314–318 (2014).

    CAS  PubMed  Google Scholar 

  20. Proksch, E., Brandner, J.M. & Jensen, J.M. The skin: an indispensable barrier. Exp. Dermatol. 17, 1063–1072 (2008).

    PubMed  Google Scholar 

  21. Feingold, K.R. Thematic review series: skin lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis. J. Lipid Res. 48, 2531–2546 (2007). This review summarizes the crucial role of lipids as cellular mortar for the barrier function of skin, and highlights their importance in inherited skin disorders.

    CAS  PubMed  Google Scholar 

  22. Feingold, K.R. & Elias, P.M. Role of lipids in the formation and maintenance of the cutaneous permeability barrier. Biochim. Biophys. Acta 1841, 280–294 (2014).

    CAS  PubMed  Google Scholar 

  23. Candi, E., Schmidt, R. & Melino, G. The cornified envelope: a model of cell death in the skin. Nat. Rev. Mol. Cell Biol. 6, 328–340 (2005).

    CAS  PubMed  Google Scholar 

  24. van Smeden, J., Janssens, M., Gooris, G.S. & Bouwstra, J.A. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim. Biophys. Acta 1841, 295–313 (2014).

    CAS  PubMed  Google Scholar 

  25. Bragulla, H.H. & Homberger, D.G. Structure and functions of keratin proteins in simple, stratified, keratinized and cornified epithelia. J. Anat. 214, 516–559 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Feingold, K.R. The regulation and role of epidermal lipid synthesis. Adv. Lipid Res. 24, 57–82 (1991).

    CAS  PubMed  Google Scholar 

  27. Ovaere, P., Lippens, S., Vandenabeele, P. & Declercq, W. The emerging roles of serine protease cascades in the epidermis. Trends Biochem. Sci. 34, 453–463 (2009).

    CAS  PubMed  Google Scholar 

  28. Elias, P.M. et al. Basis for abnormal desquamation and permeability barrier dysfunction in RXLI. J. Invest. Dermatol. 122, 314–319 (2004).

    CAS  PubMed  Google Scholar 

  29. Hansen, H.S. & Jensen, B. Essential function of linoleic acid esterified in acylglucosylceramide and acylceramide in maintaining the epidermal water permeability barrier. Evidence from feeding studies with oleate, linoleate, arachidonate, columbinate and alpha-linolenate. Biochim. Biophys. Acta 834, 357–363 (1985).

    CAS  PubMed  Google Scholar 

  30. Wertz, P.W., Cho, E.S. & Downing, D.T. Effect of essential fatty acid deficiency on the epidermal sphingolipids of the rat. Biochim. Biophys. Acta 753, 350–355 (1983).

    CAS  PubMed  Google Scholar 

  31. Elias, P.M. et al. Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis. J. Clin. Invest. 74, 1414–1421 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Schurer, N.Y. & Elias, P.M. The biochemistry and function of stratum corneum lipids. Adv. Lipid Res. 24, 27–56 (1991).

    CAS  PubMed  Google Scholar 

  33. Zeeuwen, P.L. Epidermal differentiation: the role of proteases and their inhibitors. Eur. J. Cell Biol. 83, 761–773 (2004).

    CAS  PubMed  Google Scholar 

  34. Madison, K.C. Barrier function of the skin: “la raison d'etre” of the epidermis. J. Invest. Dermatol. 121, 231–241 (2003).

    CAS  PubMed  Google Scholar 

  35. Holleran, W.M. et al. Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease. J. Clin. Invest. 93, 1756–1764 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Schmuth, M. et al. Permeability barrier disorder in Niemann-Pick disease: sphingomyelin-ceramide processing required for normal barrier homeostasis. J. Invest. Dermatol. 115, 459–466 (2000).

    CAS  PubMed  Google Scholar 

  37. Mao-Qiang, M., Feingold, K.R., Jain, M. & Elias, P.M. Extracellular processing of phospholipids is required for permeability barrier homeostasis. J. Lipid Res. 36, 1925–1935 (1995).

    CAS  PubMed  Google Scholar 

  38. Lopez-Pajares, V., Yan, K., Zarnegar, B.J., Jameson, K.L. & Khavari, P.A. Genetic pathways in disorders of epidermal differentiation. Trends Genet. 29, 31–40 (2013).

    CAS  PubMed  Google Scholar 

  39. Elias, P.M., Williams, M.L., Holleran, W.M., Jiang, Y.J. & Schmuth, M. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. J. Lipid Res. 49, 697–714 (2008).

    CAS  PubMed  Google Scholar 

  40. Gupta, L.K. & Singhi, M.K. Wood's lamp. Indian J. Dermatol. Venereol. Leprol. 70, 131–135 (2004).

    CAS  PubMed  Google Scholar 

  41. Schäfer, M. & Werner, S. Cancer as an overhealing wound: an old hypothesis revisited. Nat. Rev. Mol. Cell Biol. 9, 628–638 (2008).

    PubMed  Google Scholar 

  42. Jensen, M.A., Wilkinson, J.E. & Krainer, A.R. Splicing factor SRSF6 promotes hyperplasia of sensitized skin. Nat. Struct. Mol. Biol. 21, 189–197 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Sundaram, G.M. et al. 'See-saw' expression of microRNA-198 and FSTL1 from a single transcript in wound healing. Nature 495, 103–106 (2013).

    CAS  PubMed  Google Scholar 

  44. Rinn, J.L. et al. A systems biology approach to anatomic diversity of skin. J. Invest. Dermatol. 128, 776–782 (2008).

    CAS  PubMed  Google Scholar 

  45. Driskell, R.R. et al. Distinct fibroblast lineages determine dermal architecture in skin development and repair. Nature 504, 277–281 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Bryan, N. et al. Reactive oxygen species (ROS)–a family of fate deciding molecules pivotal in constructive inflammation and wound healing. Eur. Cell. Mater. 24, 249–265 (2012).

    CAS  PubMed  Google Scholar 

  47. Pillai, S., Oresajo, C. & Hayward, J. Ultraviolet radiation and skin aging: roles of reactive oxygen species, inflammation and protease activation, and strategies for prevention of inflammation-induced matrix degradation–a review. Int. J. Cosmet. Sci. 27, 17–34 (2005).

    CAS  PubMed  Google Scholar 

  48. Takashima, A. & Bergstresser, P.R. Impact of UVB radiation on the epidermal cytokine network. Photochem. Photobiol. 63, 397–400 (1996).

    CAS  PubMed  Google Scholar 

  49. Cadet, J., Douki, T., Ravanat, J.L. & Di Mascio, P. Sensitized formation of oxidatively generated damage to cellular DNA by UVA radiation. Photochem. Photobiol. Sci. 8, 903–911 (2009).

    CAS  PubMed  Google Scholar 

  50. 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).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Denat, L., Kadekaro, A.L., Marrot, L., Leachman, S.A. & Abdel-Malek, Z.A. Melanocytes as Instigators and victims of oxidative stress. J. Invest. Dermatol. 134, 1512–1518 (2014). In this review of the current understanding of oxidative stress and mitigating pathways that are operational in skin, the role of ROS generation is discussed in the context of vitiligo and cancer.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Mitra, D. et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background. Nature 491, 449–453 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Berger, M.F. et al. Melanoma genome sequencing reveals frequent PREX2 mutations. Nature 485, 502–506 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Lai-Cheong, J.E. et al. Loss-of-function FERMT1 mutations in kindler syndrome implicate a role for fermitin family homolog-1 in integrin activation. Am. J. Pathol. 175, 1431–1441 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Bickers, D.R. & Athar, M. Oxidative stress in the pathogenesis of skin disease. J. Invest. Dermatol. 126, 2565–2575 (2006).

    CAS  PubMed  Google Scholar 

  56. Natarajan, V.T. et al. Transcriptional upregulation of Nrf2-dependent phase II detoxification genes in the involved epidermis of vitiligo vulgaris. J. Invest. Dermatol. 130, 2781–2789 (2010). This study ascertains the role of oxidative stress in vitiligo and provides molecular understanding of differences in redox perturbations in the two epidermal cell types.

    CAS  PubMed  Google Scholar 

  57. Cavarra, E. et al. UVA light stimulates the production of cathepsin G and elastase-like enzymes by dermal fibroblasts: a possible contribution to the remodeling of elastotic areas in sun-damaged skin. Biol. Chem. 383, 199–206 (2002).

    CAS  PubMed  Google Scholar 

  58. Fagot, D., Asselineau, D. & Bernerd, F. Direct role of human dermal fibroblasts and indirect participation of epidermal keratinocytes in MMP-1 production after UV-B irradiation. Arch. Dermatol. Res. 293, 576–583 (2002).

    CAS  PubMed  Google Scholar 

  59. Quan, T., He, T., Voorhees, J.J. & Fisher, G.J. Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1 in human skin fibroblasts. J. Biol. Chem. 280, 8079–8085 (2005).

    CAS  PubMed  Google Scholar 

  60. Raposo, G. & Marks, M.S. Melanosomes—dark organelles enlighten endosomal membrane transport. Nat. Rev. Mol. Cell Biol. 8, 786–797 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Wasmeier, C., Hume, A.N., Bolasco, G. & Seabra, M.C. Melanosomes at a glance. J. Cell Sci. 121, 3995–3999 (2008).

    CAS  PubMed  Google Scholar 

  62. Urabe, K. et al. The inherent cytotoxicity of melanin precursors: a revision. Biochim. Biophys. Acta 1221, 272–278 (1994).

    CAS  PubMed  Google Scholar 

  63. Raposo, G. & Marks, M.S. The dark side of lysosome-related organelles: specialization of the endocytic pathway for melanosome biogenesis. Traffic 3, 237–248 (2002).

    PubMed  Google Scholar 

  64. Fowler, D.M. et al. Functional amyloid formation within mammalian tissue. PLoS Biol. 4, e6 (2006).

    PubMed  Google Scholar 

  65. Theos, A.C., Truschel, S.T., Raposo, G. & Marks, M.S. The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function. Pigment Cell Res. 18, 322–336 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Sturm, R.A., Box, N.F. & Ramsay, M. Human pigmentation genetics: the difference is only skin deep. Bioessays 20, 712–721 (1998).

    CAS  PubMed  Google Scholar 

  67. Steingrímsson, E., Copeland, N.G. & Jenkins, N.A. Melanocytes and the microphthalmia transcription factor network. Annu. Rev. Genet. 38, 365–411 (2004).

    PubMed  Google Scholar 

  68. Vachtenheim, J. & Borovansky, J. “Transcription physiology” of pigment formation in melanocytes: central role of MITF. Exp. Dermatol. 19, 617–627 (2010).

    CAS  PubMed  Google Scholar 

  69. Borovanský, J. & Elleder, M. Melanosome degradation: fact or fiction. Pigment Cell Res. 16, 280–286 (2003).

    PubMed  Google Scholar 

  70. Moan, J., Nielsen, K.P. & Juzeniene, A. Immediate pigment darkening: its evolutionary roles may include protection against folate photosensitization. FASEB J. 26, 971–975 (2012).

    CAS  PubMed  Google Scholar 

  71. Wicks, N.L., Chan, J.W., Najera, J.A., Ciriello, J.M. & Oancea, E. UVA phototransduction drives early melanin synthesis in human melanocytes. Curr. Biol. 21, 1906–1911 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Bellono, N.W., Kammel, L.G., Zimmerman, A.L. & Oancea, E. UV light phototransduction activates transient receptor potential A1 ion channels in human melanocytes. Proc. Natl. Acad. Sci. USA 110, 2383–2388 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Yamaguchi, Y. & Hearing, V.J. Physiological factors that regulate skin pigmentation. Biofactors 35, 193–199 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Cui, R. et al. Central role of p53 in the suntan response and pathologic hyperpigmentation. Cell 128, 853–864 (2007). This milestone study revealed the central guardian of the genome, p53 to function as a sensor and effector for UV pigmentation through the transcriptional upregulation of POMC gene that codes for the central melanogenesis factor MSH.

    CAS  PubMed  Google Scholar 

  75. Yang, G. et al. Inhibition of PAX3 by TGF-beta modulates melanocyte viability. Mol. Cell 32, 554–563 (2008).

    PubMed  Google Scholar 

  76. Yamaguchi, Y. et al. Dickkopf 1 (DKK1) regulates skin pigmentation and thickness by affecting Wnt/beta-catenin signaling in keratinocytes. FASEB J. 22, 1009–1020 (2008).

    CAS  PubMed  Google Scholar 

  77. Novák, B. & Tyson, J.J. Design principles of biochemical oscillators. Nat. Rev. Mol. Cell Biol. 9, 981–991 (2008).

    PubMed  PubMed Central  Google Scholar 

  78. Natarajan, V.T. et al. IFN-gamma signaling maintains skin pigmentation homeostasis through regulation of melanosome maturation. Proc. Natl. Acad. Sci. USA 111, 2301–2306 (2014). This recent study identified IFN-γ as a hypopigmenting factor by stalling melanosome maturation process and established a physiological and pathological relevance of this effect in multiple models.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Zaidi, M.R. et al. Interferon-gamma links ultraviolet radiation to melanomagenesis in mice. Nature 469, 548–553 (2011). This study unraveled the molecular basis to melanoma formation in response to UV light, and provides a link between the immune system and skin cancer formation.

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Carroll, J.M., Crompton, T., Seery, J.P. & Watt, F.M. Transgenic mice expressing IFN-gamma in the epidermis have eczema, hair hypopigmentation, and hair loss. J. Invest. Dermatol. 108, 412–422 (1997).

    CAS  PubMed  Google Scholar 

  81. Choi, H. et al. IL-4 inhibits the melanogenesis of normal human melanocytes through the JAK2-STAT6 signaling pathway. J. Invest. Dermatol. 133, 528–536 (2013).

    CAS  PubMed  Google Scholar 

  82. Solano, F., Briganti, S., Picardo, M. & Ghanem, G. Hypopigmenting agents: an updated review on biological, chemical and clinical aspects. Pigment Cell Res. 19, 550–571 (2006).

    CAS  PubMed  Google Scholar 

  83. Wang, C.Q. et al. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLoS ONE 6, e18907 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Rashighi, M. et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci. Transl. Med. 6, 223ra23 (2014).

    PubMed  PubMed Central  Google Scholar 

  85. Malhotra, N. & Dytoc, M. The pathogenesis of vitiligo. J. Cutan. Med. Surg. 17, 153–172 (2013).

    CAS  PubMed  Google Scholar 

  86. Guerra, L., Dellambra, E., Brescia, S. & Raskovic, D. Vitiligo: pathogenetic hypotheses and targets for current therapies. Curr. Drug Metab. 11, 451–467 (2010).

    CAS  PubMed  Google Scholar 

  87. Le Poole, I.C. & Luiten, R.M. Autoimmune etiology of generalized vitiligo. Curr. Dir. Autoimmun. 10, 227–243 (2008).

    CAS  PubMed  Google Scholar 

  88. Singh, A. et al. HLA alleles and amino-acid signatures of the peptide-binding pockets of HLA molecules in vitiligo. J. Invest. Dermatol. 132, 124–134 (2012).

    CAS  PubMed  Google Scholar 

  89. Westerhof, W., Manini, P., Napolitano, A. & d'Ischia, M. The haptenation theory of vitiligo and melanoma rejection: a close-up. Exp. Dermatol. 20, 92–96 (2011).

    CAS  PubMed  Google Scholar 

  90. Schallreuter, K.U. et al. Butyrylcholinesterase is present in the human epidermis and is regulated by H2O2: more evidence for oxidative stress in vitiligo. Biochem. Biophys. Res. Commun. 349, 931–938 (2006).

    CAS  PubMed  Google Scholar 

  91. Jin, Y. et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat. Genet. 44, 676–680 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Spritz, R.A. The genetics of generalized vitiligo. Curr. Dir. Autoimmun. 10, 244–257 (2008).

    CAS  PubMed  Google Scholar 

  93. Ortonne, J.P. & Bose, S.K. Vitiligo: where do we stand? Pigment Cell Res. 6, 61–72 (1993).

    CAS  PubMed  Google Scholar 

  94. Le Poole, I.C., Das, P.K., van den Wijngaard, R.M., Bos, J.D. & Westerhof, W. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp. Dermatol. 2, 145–153 (1993).

    CAS  PubMed  Google Scholar 

  95. Schallreuter, K.U. et al. Vitiligo pathogenesis: autoimmune disease, genetic defect, excessive reactive oxygen species, calcium imbalance, or what else? Exp. Dermatol. 17, 139–160 (2008). These two papers (refs. 94 and 95) summarize the caveats in interpreting the observations on vitiligo in light of one theory and propose interplay of several confounding factors in vitiligo etiopathogenesis.

    CAS  PubMed  Google Scholar 

  96. Teulings, H.E. et al. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: a survey among 1307 patients and their partners. Br. J. Dermatol. 168, 162–171 (2013).

    CAS  PubMed  Google Scholar 

  97. Kaidbey, K.H., Agin, P.P., Sayre, R.M. & Kligman, A.M. Photoprotection by melanin–a comparison of black and Caucasian skin. J. Am. Acad. Dermatol. 1, 249–260 (1979).

    CAS  PubMed  Google Scholar 

  98. Kollias, N., Sayre, R.M., Zeise, L. & Chedekel, M.R. Photoprotection by melanin. J. Photochem. Photobiol. B 9, 135–160 (1991).

    CAS  PubMed  Google Scholar 

  99. Chou, W.C. et al. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat. Med. 19, 924–929 (2013).

    CAS  PubMed  Google Scholar 

  100. Grimes, P.E. Psoralen photochemotherapy for vitiligo. Clin. Dermatol. 15, 921–926 (1997).

    CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by grant (TOUCH-BSC0302). P.G., A.R. and R.G. are supported by the Council for Scientific and Industrial Research (CSIR), India. We acknowledge CSIR and Department of Biotechnology for institutional support to CSIR-Institute of Genomics and Integrative Biology and National Institute of Immunology, respectively.

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  1. Council for Scientific and Industrial Research (CSIR) Institute of Genomics and Integrative Biology, Delhi, India

    Vivek T Natarajan, Amrita Ramkumar, Ritika Grover & Rajesh S Gokhale

  2. Academy of Scientific and Innovative Research, New Delhi, India

    Vivek T Natarajan, Amrita Ramkumar, Ritika Grover & Rajesh S Gokhale

  3. National Institute of Immunology, New Delhi, India

    Parul Ganju & Rajesh S Gokhale

  4. Jawaharlal Nehru Centre for Advanced Scientific Research, Bangalore, India

    Rajesh S Gokhale

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R.S.G. is the co-founder director on the board of Vyome Biosciences, a biopharmaceutical company in the area of dermatology.

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Natarajan, V., Ganju, P., Ramkumar, A. et al. Multifaceted pathways protect human skin from UV radiation. Nat Chem Biol 10, 542–551 (2014). https://doi.org/10.1038/nchembio.1548

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