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Cited by 176melanin and skin pigmentationT-cell and B-cell ImmunologyMelanoma and MAPK Pathways

Perspectives of New Advances in the Pathogenesis of Vitiligo: From Oxidative Stress to Autoimmunity

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Wang, Yinghan, Li, Shuli, Li, Chunying·2019·Medical Science Monitor
DOI 10.12659/msm.914898PMC PMC6373225
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Abstract

Vitiligo is an autoimmune cutaneous disease in which melanocytes are destroyed by CD8⁺ T cells resulting in disfiguring white spots. From the very beginning of the disease, oxidative stress plays a significant role in promoting the onset of vitiligo, as noted by many studies. Multiple factors lead to the overproduction of reactive oxygen species (ROS), and collaboratively cause ROS accumulation in vulnerable melanocytes. However, ROS are responsible for melanocyte damage manifested by the level of molecules, organelles, and cells, and the generation of autoantigens, through different pathways related to the dysregulation of melanocytes. Recent studies have shown that presentation of autoantigens is mediated by innate immunity, which bridges the gap between oxidative stress and adaptive immunity. The recruitment of CD8⁺ T cells induced by cytokines and chemokines guarantees the final destruction of epidermal melanocytes. Moreover, emerging concerns regarding regulatory T cells and resident memory T cells help explain the reinstatement and relapse of vitiligo. Here, we provide new perspectives in the advances in understanding of this disease pathogenesis and we attempt to find more interrelationships between oxidative stress and autoimmunity.

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  • Oxidative stress caused by H2O2 is a major contributor to the onset and progression of vitiligo.

    “Evidence shows that oxidative stress caused by H2O2 is a major contributor to the onset and progression of vitiligo. 83”

    From Therapeutic Properties and Pharmacological Activities of Asiaticoside and Madecassoside: A Review (2023) · cites this paper as [83]

    The Background describes oxidative stress as a possible essential factor in vitiligo pathogenesis, and the Consequences of Excessive ROS sections describe ways H2O2 can disrupt melanin synthesis and promote melanocyte apoptosis. The paper does not establish that H2O2-driven stress is a major contributor to both the onset and progression of vitiligo; that wording is more definite and specific than the passages support. Page numbers were not provided in our copy. (LLM, conf=0.82)

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  1. [1]Picardo M Dell’Anna ML Ezzedine K Vitiligo Nat Rev Dis Primers 2015 341 1 15011 27189851
  2. [2]Xie H Zhou F Liu L Vitiligo: How do oxidative stress-induced autoantigens trigger autoimmunity? J Dermatol Sci 2016 81 1 3 9 26387449
  3. [3]Richmond JM Frisoli ML Harris JE Innate immune mechanisms in vitiligo: danger from within Curr Opin Immunol 2013 25 6 676 82 24238922 PMC3935321
  4. [4]Ezzedine K Eleftheriadou V Whitton M Vitiligo Lancet 2015 386 9988 74 84 25596811
  5. [5]Puri N Mojamdar M Ramaiah A In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects J Invest Dermatol 1987 88 4 434 38 3559270
  6. [6]Jimbow K Chen H Park JS Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo Br J Dermatol 2001 144 1 55 65 11167683
  7. [7]He Y Li S Zhang W Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo Sci Rep 2017 7 42394 28186139 PMC5301258
  8. [8]Al-Shobaili HA Rasheed Z Oxidized tyrosinase: A possible antigenic stimulus for non-segmental vitiligo autoantibodies J Dermatol Sci 2015 79 3 203 13 26137927
  9. [9]Denat L Kadekaro AL Marrot L Melanocytes as instigators and victims of oxidative stress J Invest Dermatol 2014 134 6 1512 18 24573173 PMC4418514
  10. [10]Laddha NC Dwivedi M Mansuri MS Vitiligo: Interplay between oxidative stress and immune system Exp Dermatol 2013 22 4 245 50 23425123
  11. [11]Dell’Anna ML Ottaviani M Albanesi V Membrane lipid alterations as a possible basis for melanocyte degeneration in vitiligo J Invest Dermatol 2007 127 5 1226 33 17235326
  12. [12]Dell’Anna ML Ottaviani M Bellei B Membrane lipid defects are responsible for the generation of reactive oxygen species in peripheral blood mononuclear cells from vitiligo patients J Cell Physiol 2010 223 1 187 93 20049874
  13. [13]Dell’Anna ML Urbanelli S Mastrofrancesco A Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients Pigment Cell Res 2003 16 5 553 59 12950736
  14. [14]AlGhamdi KM Kumar A Depigmentation therapies for normal skin in vitiligo universalis J Eur Acad Dermatol Venereol 2011 25 7 749 57 21054565
  15. [15]van den Boorn JG Picavet DI van Swieten PF Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy J Invest Dermatol 2011 131 6 1240 51 21326294
  16. [16]Lei XG Zhu JH Cheng WH Paradoxical roles of antioxidant enzymes: Basic mechanisms and health implications Physiol Rev 2016 96 1 307 64 26681794 PMC4839492
  17. [17]Waterham HR Ferdinandusse S Wanders RJ Human disorders of peroxisome metabolism and biogenesis Biochim Biophys Acta 2016 1863 5 922 33 26611709
  18. [18]Boissy RE Manga P On the etiology of contact/occupational vitiligo Pigment Cell Res 2004 17 3 208 14 15140065
  19. [19]Song P Li K Liu L Genetic polymorphism of the Nrf2 promoter region is associated with vitiligo risk in Han Chinese populations J Cell Mol Med 2016 20 10 1840 50 27222475 PMC5020638
  20. [20]Jian Z Li K Song P Impaired activation of the Nrf2-ARE signaling pathway undermines H2O2-induced oxidative stress response: A possible mechanism for melanocyte degeneration in vitiligo J Invest Dermatol 2014 134 8 2221 30 24662764
  21. [21]Chang Y Li S Guo W Simvastatin protects human melanocytes from H2O2-induced oxidative stress by activating Nrf2 J Invest Dermatol 2017 137 6 1286 96 28174051
  22. [22]Jian Z Tang L Yi X Aspirin induces Nrf2-mediated transcriptional activation of haem oxygenase-1 in protection of human melanocytes from H2O2-induced oxidative stress J Cell Mol Med 2016 20 7 1307 18 26969214 PMC4929306
  23. [23]Ma J Li S Zhu L Baicalein protects human vitiligo melanocytes from oxidative stress through activation of NF-E2-related factor2 (Nrf2) signaling pathway Free Radic Biol Med 2018 129 492 503 30342186
  24. [24]Bickers DR Athar M Oxidative stress in the pathogenesis of skin disease J Invest Dermatol 2006 126 12 2565 75 17108903
  25. [25]Salem MM Shalbaf M Gibbons NC Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: A possible repair mechanism for DNA damage FASEB J 2009 23 11 3790 807 19641144
  26. [26]Vaseghi H Houshmand M Jadali Z Increased levels of mitochondrial DNA copy number in patients with vitiligo Clin Exp Dermatol 2017 42 7 749 54 28866865
  27. [27]Wei C Jian Z Wang L Genetic variants of the APE1 gene and the risk of vitiligo in a Chinese population: A genotype–phenotype correlation study Free Radic Biol Med 2013 58 5 64 72 23369758
  28. [28]Hasse S Gibbons NC Rokos H Perturbed 6-tetrahydrobiopterin recycling via decreased dihydropteridine reductase in vitiligo: More evidence for H2O2 stress J Invest Dermatol 2004 122 2 307 13 15009710
  29. [29]Schallreuter KU Elwary SMA Gibbons NC Activation/deactivation of acetylcholinesterase by H2O2: More evidence for oxidative stress in vitiligo Biochem Biophys Res Commun 2004 315 2 502 8 14766237
  30. [30]Zhang Y Liu L Jin L Oxidative stress-induced calreticulin expression and translocation: New insights into the destruction of melanocytes J Invest Dermatol 2014 134 1 183 91 23771121
  31. [31]Kang P Zhang W Chen X TRPM2 mediates mitochondria-dependent apoptosis of melanocytes under oxidative stress Free Radic Biol Med 2018 126 259 68 30138713
  32. [32]Passeron T Ortonne JP Activation of the unfolded protein response in vitiligo: The missing link? J Invest Dermatol 2012 132 11 2502 4 23069909
  33. [33]Toosi S Orlow SJ Manga P Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8 J Invest Dermatol 2012 132 11 2601 9 22696056 PMC3443495
  34. [34]Abdallah M El-Mofty M Anbar T CXCL-10 and interleukin-6 are reliable serum markers for vitiligo activity: A multicenter cross-sectional study Pigment Cell Melanoma Res 2018 31 2 330 36 29094481
  35. [35]Li S Zhu G Yang Y Oxidative stress drives CD8(+) T-cell skin trafficking in patients with vitiligo through CXCL16 upregulation by activating the unfolded protein response in keratinocytes J Allergy Clin Immunol 2017 140 1 177 89 27826097
  36. [36]Bonecchi R Galliera E Borroni EM Chemokines and chemokine receptors: An overview Front Biosci (Landmark Ed) 2009 14 540 51 19273084
  37. [37]Ma KC Schenck EJ Pabon MA The role of danger signals in the pathogenesis and perpetuation of critical illness Am J Respir Crit Care Med 2018 197 3 300 9 28977759 PMC5811949
  38. [38]Denman CJ McCracken J Hariharan V HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo J Invest Dermatol 2008 128 8 2041 48 18337834 PMC3778919
  39. [39]Henning SW Fernandez MF Mahon JP HSP70IQ435A-encoding DNA repigments vitiligo lesions in Sinclair swine J Invest Dermatol 2018 138 12 2531 39 30031029 PMC9732057
  40. [40]Frisoli ML Harris JE Treatment with modified heat shock protein repigments vitiligo lesions in Sinclair swine J Invest Dermatol 2018 138 12 2505 6 30466536
  41. [41]Mosenson JA Flood K Klarquist J Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress Pigment Cell Melanoma Res 2014 27 2 209 20 24354861 PMC3947476
  42. [42]Mosenson JA Zloza A Klarquist J HSP70i is a critical component of the immune response leading to vitiligo Pigment Cell Melanoma Res 2012 25 1 88 98 21978301 PMC3662798
  43. [43]Mosenson JA Eby JM Hernandez C A central role for inducible heat-shock protein 70 in autoimmune vitiligo Exp Dermatol 2013 22 9 566 69 23786523 PMC3745819
  44. [44]Kroll TM Bommiasamy H Boissy RE 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: Relevance to vitiligo J Invest Dermatol 2005 124 4 798 806 15816839 PMC1747533
  45. [45]Thériault JR Mambula SS Sawamura T Extracellular HSP70 binding to surface receptors present on antigen presenting cells and endothelial/epithelial cells FEBS Lett 2005 579 9 1951 60 15792802
  46. [46]Millar DG Garza KM Odermatt B Hsp70 promotes antigen-presenting cell function and converts T-cell tolerance to autoimmunity in vivo Nat Med 2003 9 12 1469 76 14625545
  47. [47]Jacquemin C Rambert J Guillet S HSP70 potentiates interferon-alpha production by plasmacytoid dendritic cells: Relevance for cutaneous lupus and vitiligo pathogenesis Br J Dermatol 2017 177 5 1367 75 28380264
  48. [48]Denning TL Wang YC Patel SR Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses Nat Immunol 2007 8 10 1086 94 17873879
  49. [49]Benzekri L Gauthier Y Clinical markers of vitiligo activity J Am Acad Dermatol 2017 76 5 856 62 28245942
  50. [50]van den Boorn JG Konijnenberg D Dellemijn TA Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients J Invest Dermatol 2009 129 9 2220 32 19242513
  51. [51]Le Gal FA Avril MF Bosq J Direct evidence to support the role of antigen-specific CD8+ T cells in melanoma-associated vitiligo J Invest Dermatol 2001 117 6 1464 70 11886510
  52. [52]Boniface K Jacquemin C Darrigade AS Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3 J Invest Dermatol 2017 138 2 355 64 28927891
  53. [53]Rashighi M Harris JE Interfering with the IFN-gamma/CXCL10 pathway to develop new targeted treatments for vitiligo Ann Transl Med 2015 3 21 343 26734651 PMC4690998
  54. [54]Rashighi M Agarwal P Richmond JM CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo Sci Transl Med 2014 6 223 223ra23 PMC4086941 24523323
  55. [55]Wang XX Wang QQ Wu JQ Increased expression of CXCR3 and its ligands in patients with vitiligo and CXCL10 as a potential clinical marker for vitiligo Br J Dermatol 2016 174 6 1318 26 26801009
  56. [56]Harris JE Cellular stress and innate inflammation in organ-specific autoimmunity: Lessons learned from vitiligo Immunol Rev 2016 269 1 11 25 26683142 PMC4685729
  57. [57]Yang L Wei Y Sun Y Interferon-gamma inhibits melanogenesis and induces apoptosis in melanocytes: A pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo Acta Derm Venereol 2015 95 6 664 70 25721262
  58. [58]Richmond JM Masterjohn E Chu R CXCR3 depleting antibodies prevent and reverse vitiligo in mice J Invest Dermatol 2017 137 4 982 85 28126463
  59. [59]Rork JF Rashighi M Harris JE Understanding autoimmunity of vitiligo and alopecia areata Curr Opin Pediatr 2016 28 4 463 69 27191524 PMC4957563
  60. [60]Craiglow BG King BA Tofacitinib citrate for the treatment of vitiligo: A pathogenesis-directed therapy JAMA Dermatol 2015 151 10 1110 12 26107994
  61. [61]Ben Ahmed M Zaraa I Rekik R Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo Pigment Cell Melanoma Res 2012 25 1 99 109 21985183
  62. [62]Lin M Zhang BX Shen N Regulatory T cells from active non-segmental vitiligo exhibit lower suppressive ability on CD8+CLA+ T cells Eur J Dermatol 2014 24 6 676 82 25335433
  63. [63]Le Poole IC Mehrotra S Replenishing regulatory T cells to halt depigmentation in vitiligo J Invest Dermatol Symp Proc 2017 18 2 S38 45 28941492
  64. [64]Dwivedi M Kemp EH Laddha NC Regulatory T cells in vitiligo: Implications for pathogenesis and therapeutics Autoimmun Rev 2015 14 1 49 56 25308528
  65. [65]Klarquist J Denman CJ Hernandez C Reduced skin homing by functional Treg in vitiligo Pigment Cell Melanoma Res 2010 23 2 276 86 20175879 PMC3778930
  66. [66]Eby JM Kang HK Tully ST CCL22 to activate Treg migration and suppress depigmentation in vitiligo J Invest Dermatol 2015 135 6 1574 80 25634358 PMC5044299
  67. [67]Singh RK Lee KM Vujkovic-Cvijin I The role of IL-17 in vitiligo: A review Autoimmun Rev 2016 15 4 397 404 26804758 PMC4769658
  68. [68]Malik BT Byrne KT Vella JL Resident memory T cells in the skin mediate durable immunity to melanoma Sci Immunol 2017 2 10 pii: eaam6346 PMC5525335 28738020
  69. [69]Richmond JM Strassner JP Zapata L Jr Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo Sci Transl Med 2018 10 450 pii: eaam7710 PMC6495055 30021889
  70. [70]Clark RA Resident memory T cells in human health and disease Sci Transi Med 2015 7 269 269rv1 PMC4425129 25568072
  71. [71]Richmond JM Strassner JP Rashighi M Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo J Invest Dermatol 2018 [Epub ahead of print] PMC6431571 30423329
  72. [73]Pan Y Tian T Park CO Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism Nature 2017 543 7644 252 56 28219080 PMC5509051

Cited by

Sorted by citations

Authors
Wang, Y., Li, S., & Li, C.
Affiliations
Xijing Hospital (CN)
Corresponding author
  • Li, Shuli
  • Li, Chunying
ORCID
Venue
Medical Science Monitor
Publisher
International Scientific Information, Inc.
Published
2019-02-06
Volume
25
Pages
1017-1023
ISSN
  • 1234-1010 (ISSN-L)
  • 1643-3750
DOI
10.12659/msm.914898
PMC
PMC6373225
OpenAlex
W2914141644
Cited by
176
References
1
Citations by year
2026: 7 · 2025: 16 · 2024: 23 · 2023: 51 · 2022: 22 · 2021: 31 · 2020: 20 · 2019: 4 · 2018: 1
FWCI
2.26
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Medical Science Monitor (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (91742201, 81472863, 81602764)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
vitiligo, pathogenesis, oxidative stress, reactive oxygen species, melanocytes, autoimmunity, CD8+ T cells, autoantigens, innate immunity, adaptive immunity, regulatory T cells, tissue-resident memory T cells, cytokines and chemokines
MeSH terms
Antioxidants, Autoantigens, Autoimmune Diseases, Humans, Immunity, Innate, Melanocytes, Vitiligo, Autoimmunity, Cytokines, Reactive Oxygen Species, Oxidative Stress, CD8-Positive T-Lymphocytes, Adaptive Immunity

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