1932

Abstract

Vitiligo is an autoimmune disease of the skin that targets pigment-producing melanocytes and results in patches of depigmentation that are visible as white spots. Recent research studies have yielded a strong mechanistic understanding of this disease. Autoreactive cytotoxic CD8+ T cells engage melanocytes and promote disease progression through the local production of IFN-γ, and IFN-γ-induced chemokines are then secreted from surrounding keratinocytes to further recruit T cells to the skin through a positive-feedback loop. Both topical and systemic treatments that block IFN-γ signaling can effectively reverse vitiligo in humans; however, disease relapse is common after stopping treatments. Autoreactive resident memory T cells are responsible for relapse, and new treatment strategies focus on eliminating these cells to promote long-lasting benefit. Here, we discuss basic, translational, and clinical research studies that provide insight into the pathogenesis of vitiligo, and how this insight has been utilized to create new targeted treatment strategies.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-100919-023531
2020-04-26
2024-06-16
Loading full text...

Full text loading...

/deliver/fulltext/immunol/38/1/annurev-immunol-100919-023531.html?itemId=/content/journals/10.1146/annurev-immunol-100919-023531&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Barman S. 1995. Switra and its treatment in Veda. Ancient Sci. Life 15:71–74
    [Google Scholar]
  2. 2. 
    Singh G, Ansari Z, Dwivedi RN 1974. Vitiligo in ancient Indian medicine. Arch. Dermatol. 109:913
    [Google Scholar]
  3. 3. 
    Zhang Y, Cai Y, Shi M, Jiang S, Cui S et al. 2016. The prevalence of vitiligo: a meta-analysis. PLOS ONE 11:9e0163806–17
    [Google Scholar]
  4. 4. 
    Salzes C, Abadie S, Seneschal J, Whitton M, Meurant J-M et al. 2016. The Vitiligo Impact Patient scale (VIPs): development and validation of a vitiligo burden assessment tool. J. Investig. Dermatol. 136:152–58
    [Google Scholar]
  5. 5. 
    Linthorst Homan MW, Spuls PI, de Korte J, Bos JD, Sprangers MA, van der Veen JPW 2009. The burden of vitiligo: patient characteristics associated with quality of life. J. Am. Dermatol. 61:3411–20
    [Google Scholar]
  6. 6. 
    Elbuluk N, Ezzedine K. 2017. Quality of life, burden of disease, co-morbidities, and systemic effects in vitiligo patients. Dermatol. Clin. 35:2117–28
    [Google Scholar]
  7. 7. 
    Ezzedine K, Eleftheriadou V, Whitton M, van Geel N 2015. Vitiligo. Lancet 386:998874–84
    [Google Scholar]
  8. 8. 
    Frisoli ML, Harris JE. 2017. Vitiligo: Mechanistic insights lead to novel treatments. J. Allergy Clin. Immunol. 140:3654–62
    [Google Scholar]
  9. 9. 
    Nordlund JJ. 2017. The medical treatment of vitiligo. Dermatol. Clin. 35:2107–16
    [Google Scholar]
  10. 10. 
    Koranne RV, Sachdeva KG. 1988. Vitiligo. Int. J. Dermatol. 27:10676–81
    [Google Scholar]
  11. 11. 
    Ezzedine K, Harris JE. 2019. Vitiligo. Fitzpatrick's Dermatology in General Medicine S Kang, M Amagai, AL Bruckner, AH Enk, DJ Margolis et al. chap 761330–50 New York: McGraw-Hill Educ. , 9th ed..
    [Google Scholar]
  12. 12. 
    Bleehen SS. 1976. The treatment of vitiligo with topical corticosteroids. Br. J. Dermatol. 94:1–9
    [Google Scholar]
  13. 13. 
    Njoo MD, Spuls PI, Bos JD, Westerhof W, Bossuyt PMM 1998. Nonsurgical repigmentation therapies in vitiligo. Arch. Dermatol. 134:1532–40
    [Google Scholar]
  14. 14. 
    Passeron T. 2017. Medical and maintenance treatments for vitiligo. Dermatol. Clin. 35:2163–70
    [Google Scholar]
  15. 15. 
    Radakovic-Fijan S, Fürnsinn-Friedl AM, Hönigsmann H, Tanew A 2001. Oral dexamethasone pulse treatment for vitiligo. J. Am. Acad. Dermatol. 44:5814–17
    [Google Scholar]
  16. 16. 
    Kanwar AJ, Mahajan R, Parsad D 2013. Low-dose oral mini-pulse dexamethasone therapy in progressive unstable vitiligo. J. Cutan. Med. Surg. 17:4259–68
    [Google Scholar]
  17. 17. 
    Pasricha JS, Khaitan BK. 1993. Oral mini-pulse therapy with betamethasone in vitiligo patients having extensive or fast-spreading disease. Int. J. Dermatol. 32:753–57
    [Google Scholar]
  18. 18. 
    Pathak MA, Fitzpatrick TB. 1992. The evolution of photochemotherapy with psoralens and UVA (PUVA): 2000 BC to 1992 AD. J. Photochem. Photobiol. B 14:1–23–22
    [Google Scholar]
  19. 19. 
    Abdel-Naser MB, Liakou AI, Elewa R, Hippe S, Knolle J, Zouboulis CC 2016. Increased activity and number of epidermal melanocytes in lesional psoriatic skin. Dermatology 232:4425–30
    [Google Scholar]
  20. 20. 
    Westerhof W, Nieuweboer-Krobotova L. 1997. Treatment of vitiligo with UV-B radiation versus topical psoralen plus UV-A. Arch. Dermatol. 133:121525–28
    [Google Scholar]
  21. 21. 
    Yones SS, Palmer RA, Garibaldinos TM, Hawk J 2007. Randomized double-blind trial of treatment of vitiligo. Arch. Dermatol. 143:578–84
    [Google Scholar]
  22. 22. 
    Parsad D, Kanwar AJ, Kumar B 2006. Psoralen-ultraviolet A versus narrow-band ultraviolet B phototherapy for the treatment of vitiligo. J. Eur. Acad. Dermatol. Venerol. 20:2175–77
    [Google Scholar]
  23. 23. 
    Mofty ME, Mostafa W, Esmat S, Youssef R, Azzam O et al. 2006. Narrow band ultraviolet B 311 nm in the treatment of vitiligo: two right-left comparison studies. Photodermatol. Photoimmunol. Photomed. 22:16–11
    [Google Scholar]
  24. 24. 
    Bhatnagar A, Kanwar AJ, Parsad D, De D 2007. Comparison of systemic PUVA and NB-UVB in the treatment of vitiligo: an open prospective study. J. Eur. Acad. Dermatol. Venerol. 21:5638–42
    [Google Scholar]
  25. 25. 
    Esmat S, Hegazy RA, Shalaby S, Chu-Sung Hu S, Lan C-CE 2017. Phototherapy and combination therapies for vitiligo. Dermatol. Clin. 35:2171–92
    [Google Scholar]
  26. 26. 
    Poon TSC, Barnetson RSC, Halliday GM 2005. Sunlight-induced immunosuppression in humans is initially because of UVB, then UVA, followed by interactive effects. J. Investig. Dermatol. 125:4840–46
    [Google Scholar]
  27. 27. 
    Schwarz T. 2005. Mechanisms of UV-induced immunosuppression. Keio J. Med. 54:4165–71
    [Google Scholar]
  28. 28. 
    Choi W, Miyamura Y, Wolber R, Smuda C, Reinhold W et al. 2010. Regulation of human skin pigmentation in situ by repetitive UV exposure: molecular characterization of responses to UVA and/or UVB. J. Investig. Dermatol. 130:61685–96
    [Google Scholar]
  29. 29. 
    van Schanke A, Jongsma MJ, Bisschop R, van Venrooij GMCAL, Rebel H, de Gruijl FR 2005. Single UVB overexposure stimulates melanocyte proliferation in murine skin, in contrast to fractionated or UVA-1 exposure. J. Investig. Dermatol. 124:1241–47
    [Google Scholar]
  30. 30. 
    Cavalié M, Ezzedine K, Fontas E, Montaudié H, Castela E et al. 2015. Maintenance therapy of adult vitiligo with 0.1% tacrolimus ointment: a randomized, double blind, placebo-controlled study. J. Investig. Dermatol. 135:4970–74
    [Google Scholar]
  31. 31. 
    Millington GWM, Levell NJ. 2007. Vitiligo: the historical curse of depigmentation. Int. J. Dermatol. 46:990–95
    [Google Scholar]
  32. 32. 
    Puri N, Mojamdar M, Ramaiah A 1987. In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects. J. Investig. Dermatol. 88:4434–38
    [Google Scholar]
  33. 33. 
    Puri N, Mojamdar M, Ramaiah A 1989. Growth defects of melanocytes in culture from vitiligo subjects are spontaneously corrected in vivo in repigmenting subjects and can be partially corrected by the addition of fibroblast-derived growth factors in vitro. Arch. Dermatol. Res. 281:178–84
    [Google Scholar]
  34. 34. 
    Dell'Anna ML, Mastrofrancesco A, Sala R, Venturini M, Ottaviani M et al. 2007. Antioxidants and narrow band-UVB in the treatment of vitiligo: a double-blind placebo controlled trial. Clin. Exp. Dermatol. 32:631–36
    [Google Scholar]
  35. 35. 
    Schallreuter KU, Moore J, Wood JM, Beazley WD, Gaze DC et al. 1999. In vivo and in vitro evidence for hydrogen peroxide (H2O2) accumulation in the epidermis of patients with vitiligo and its successful removal by a UVB-activated pseudocatalase. J. Investig. Dermatol. Symp. Proc. 4:191–96
    [Google Scholar]
  36. 36. 
    Medrano EE, Nordlund JJ. 1990. Successful culture of adult human melanocytes obtained from normal and vitiligo donors. J. Investig. Dermatol. 95:441–45
    [Google Scholar]
  37. 37. 
    Maresca V, Roccella M, Roccella F, Camera E, Del Porto G et al. 1997. Increased sensitivity to peroxidative agents as a possible pathogenic factor of melanocyte damage in vitiligo. J. Investig. Dermatol. 109:3310–13
    [Google Scholar]
  38. 38. 
    Jimbow K, Chen H, Park J-S, Thomas PD 2000. Increased sensitivity of melanocytes to oxidative stress and abnormal expression of tyrosinase-related protein in vitiligo. Br. J. Dermatol. 144:55–65
    [Google Scholar]
  39. 39. 
    Shalbaf M, Gibbons NCJ, Wood JM, Maitland DJ, Rokos H et al. 2008. Presence of epidermal allantoin further supports oxidative stress in vitiligo. Exp. Dermatol. 17:9761–70
    [Google Scholar]
  40. 40. 
    Koca R, Armutcu F, Altinyazar C, Gurel A 2004. Oxidant-antioxidant enzymes and lipid peroxidation in generalized vitiligo. Exp. Dermatol. 29:406–9
    [Google Scholar]
  41. 41. 
    Dell'Anna ML, Ottaviani M, Albanesi V, Vidolin AP, Leone G et al. 2007. Membrane lipid alterations as a possible basis for melanocyte degeneration in vitiligo. J. Investig. Dermatol. 127:51226–33
    [Google Scholar]
  42. 42. 
    Gawkrodger DJ. 2009. Pseudocatalase and narrowband ultraviolet B for vitiligo: clearing the picture. Br. J. Dermatol. 161:4721–22
    [Google Scholar]
  43. 43. 
    Gilhar A, Pillar T, Eidelman S, Etzioni A 1989. Vitiligo and idiopathic guttate hypomelanosis: repigmentation of skin following engraftment onto nude mice. Arch. Dermatol. 125:1363–66
    [Google Scholar]
  44. 44. 
    Stuttgen G. 1950. Die vitiligo in erbbiologischer betrachtung. Z. Haut Geschlechtskr. 9:451–57
    [Google Scholar]
  45. 45. 
    Teindel H. 1950. Familiare vitiligo. Z. Haut Geschlechtskr. 9:457–62
    [Google Scholar]
  46. 46. 
    Spritz RA, Andersen GHL. 2017. Genetics of vitiligo. Dermatol. Clin. 35:2245–55
    [Google Scholar]
  47. 47. 
    Alkhateeb A, Fain PR, Thody A, Bennett DC, Spritz RA 2003. Epidemiology of vitiligo and associated autoimmune diseases in Caucasian probands and their families. Pigment Cell Res 16:3208–14
    [Google Scholar]
  48. 48. 
    Hafez M, Sharaf L, Abd el-Nabi SM 1983. The genetics of vitiligo. Acta Derm. Venerol. 63:249–51
    [Google Scholar]
  49. 49. 
    Das SK, Majumder PP, Majumdar TK, Haldar B 1985. Studies on vitiligo. II. Familial aggregation and genetics. Genet. Epidemiol. 2:255–62
    [Google Scholar]
  50. 50. 
    Hadi A, Wang JF, Uppal P, Penn LA, Elbuluk N 2020. Comorbid diseases of vitiligo: a 10-year cross-sectional retrospective study of an urban US population. J. Am. Acad. Dermatol. 82:3628–33
    [Google Scholar]
  51. 51. 
    Gill L, Zarbo A, Isedeh P, Jacobsen G, Lim HW, Hamzavi I 2016. Comorbid autoimmune diseases in patients with vitiligo: a cross-sectional study. J. Am. Dermatol. 74:2295–302
    [Google Scholar]
  52. 52. 
    Li Z, Ren J, Niu X, Xu Q, Wang X et al. 2016. Meta-analysis of the association between vitiligo and human leukocyte antigen-A. BioMed. Res. Int. 2016 51–13
    [Google Scholar]
  53. 53. 
    Roberts GHL, Paul S, Yorgov D, Santorico SA, Spritz RA 2019. Family clustering of autoimmune vitiligo results principally from polygenic inheritance of common risk alleles. Am. J. Hum. Genet. 105:2364–72
    [Google Scholar]
  54. 54. 
    Naughton GK, Eisinger M, Bystryn J-C 1983. Antibodies to normal human melanocytes in vitiligo. J. Exp. Med. 158:246–51
    [Google Scholar]
  55. 55. 
    Cui J, Arita Y, Bystryn J-C 1993. Cytolytic antibodies to melanocytes in vitiligo. J. Investig. Dermatol. 100:6812–15
    [Google Scholar]
  56. 56. 
    Gilhar A, Zelickson B, Ulman Y, Etzioni A 1995. In vivo destruction of melanocytes by the IgG fraction of serum from patients with vitiligo. J. Investig. Dermatol. 105:5683–86
    [Google Scholar]
  57. 57. 
    Merimsky O, Shoenfeld Y, Baharav E, Altomonte M, Chaitchik S et al. 1996. Melanoma-associated hypopigmentation: Where are the antibodies. ? Am. J. Clin. Oncol. 19:6613–18
    [Google Scholar]
  58. 58. 
    Kroon MW, Kemp EH, Wind BS, Krebbers G, Bos JD et al. 2012. Melanocyte antigen-specific antibodies cannot be used as markers for recent disease activity in patients with vitiligo. J. Eur. Acad. Dermatol. Venerol. 27:91172–75
    [Google Scholar]
  59. 59. 
    Badri AMTA, Todd PM, Garioch JJ, Gudgeon JE, Stewart DG, Goudie RB 1993. An immunohistological study of cutaneous lymphocytes in vitiligo. J. Pathol. 170:149–55
    [Google Scholar]
  60. 60. 
    Le Poole IC, van den Wijngaard RM, Westerhof W, Das P 1996. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am. J. Pathol 148:1219–28
    [Google Scholar]
  61. 61. 
    Ahn SK, Choi EH, Lee SH, Won JH, Hann SK, Park Y-K 1994. Immunohistochemical studies from vitiligo. Yonsei Med. J. 35:404–10
    [Google Scholar]
  62. 62. 
    Wankowicz-Kalinska A, van den Wijngaard RMJGJ, Tigges BJ, Westerhof W, Ogg GS et al. 2003. Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo. Lab. Investig. 83:5683–95
    [Google Scholar]
  63. 63. 
    Strassner JP, Rashighi M, Ahmed Refat M, Richmond JM, Harris JE 2017. Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity. J. Am. Dermatol. 76:5847–855.e5
    [Google Scholar]
  64. 64. 
    Kirkin AF, Dzhandzhugazyan K, Zeuthen J 1998. Melanoma-associated antigens recognized by cytotoxic T lymphocytes. AMPIS 106:665–79
    [Google Scholar]
  65. 65. 
    Ogg GS, Dunbar PR, Romero P, Chen J-L, Cerundolo V 1998. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J. Exp. Med. 21:1203–8
    [Google Scholar]
  66. 66. 
    Palermo B, Campanelli R, Garbelli S, Mantovani S, Lantelme E et al. 2001. Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo. J. Investig. Dermatol. 117:2326–32
    [Google Scholar]
  67. 67. 
    van den Boorn JG, Konijnenberg D, Dellemijn TAM, van der Veen JPW, Bos JD et al. 2009. Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients. J. Investig. Dermatol. 129:92220–32
    [Google Scholar]
  68. 68. 
    Edwards J, Wilmott JS, Madore J, Gide TN, Quek C et al. 2018. CD103+ Tumor-resident CD8+ T cells are associated with improved survival in immunotherapy-naive melanoma patients and expand significantly during anti-PD-1 treatment. Clin. Cancer Res. 24:3036–45
    [Google Scholar]
  69. 69. 
    Wu R, Forget M-A, Chacon J, Bernatchez C, Haymaker C et al. 2012. Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma. Cancer J 18:2160–75
    [Google Scholar]
  70. 70. 
    Martinez-Lostao L, Anel A, Pardo J 2015. How do cytotoxic lymphocytes kill cancer cells. ? Clin. Cancer Res. 21:225047–56
    [Google Scholar]
  71. 71. 
    Teulings H-E, Limpens J, Jansen SN, Zwinderman AH, Reitsma JB et al. 2015. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. JCO 33:7773–81
    [Google Scholar]
  72. 72. 
    Yee C, Thompson JA, Roche P, Byrd DR, Lee PP et al. 2000. Melanocyte destruction after antigen-specific immunotherapy of melanoma. J. Exp. Med. 192:111637–44
    [Google Scholar]
  73. 73. 
    Grimes PE, Morris R, Avaniss-Aghajani E, Soriano T, Meraz M, Metzger A 2004. Topical tacrolimus therapy for vitiligo: therapeutic responses and skin messenger RNA expression of proinflammatory cytokines. J. Am. Acad. Dermatol. 51:152–61
    [Google Scholar]
  74. 74. 
    Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K et al. 2014. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci. Transl. Med. 6:223223ra23
    [Google Scholar]
  75. 75. 
    Bertolotti A, Boniface K, Vergier B, Mossalayi D, Taïeb A et al. 2014. Type I interferon signature in the initiation of the immune response in vitiligo. Pigment Cell Melanoma Res 27:3398–407
    [Google Scholar]
  76. 76. 
    Wang XX, Wang QQ, Wu JQ, Jiang M, Chen L et al. 2016. Increased expression of CXCR3 and its ligands in patients with vitiligo and CXCL10 as a potential clinical marker for vitiligo. Br. J. Dermatol. 174:61190–91
    [Google Scholar]
  77. 77. 
    Boniface K, Jacquemin C, Darrigade A-S, Dessarthe B, Martins C et al. 2018. Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3. J. Investig. Dermatol. 138:2355–64
    [Google Scholar]
  78. 78. 
    Gregg RK, Nichols L, Chen Y, Lu B, Engelhard VH 2010. Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase-specific TCR transgenic mice. J. Immunol. 184:41909–17
    [Google Scholar]
  79. 79. 
    Amos SM, Pegram HJ, Westwood JA, John LB, Devaud C et al. 2011. Adoptive immunotherapy combined with intratumoral TLR agonist delivery eradicates established melanoma in mice. Cancer Immunol. Immunother. 60:5671–83
    [Google Scholar]
  80. 80. 
    Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA 2012. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8+ T-cell accumulation in the skin. J. Investig. Dermatol. 132:71869–76
    [Google Scholar]
  81. 81. 
    Richmond JM, Bangari DS, Essien KI, Currimbhoy SD, Groom JR et al. 2017. Keratinocyte-derived chemokines orchestrate T-cell positioning in the epidermis during vitiligo and may serve as biomarkers of disease. J. Investig. Dermatol. 137:2350–58
    [Google Scholar]
  82. 82. 
    Richmond JM, Masterjohn E, Chu R, Tedstone J, Youd ME, Harris JE 2017. CXCR3 depleting antibodies prevent and reverse vitiligo in mice. J. Investig. Dermatol. 137:4982–85
    [Google Scholar]
  83. 83. 
    Damsky W, King BA. 2017. JAK inhibitors in dermatology: The promise of a new drug class. J. Am. Dermatol. 76:4736–44
    [Google Scholar]
  84. 84. 
    Jackson SW, Jacobs HM, Arkatkar T, Dam EM, Scharping NE et al. 2016. B cell IFN-γ receptor signaling promotes autoimmune germinal centers via cell-intrinsic induction of BCL-6. J. Exp. Med. 213:5733–50
    [Google Scholar]
  85. 85. 
    Craiglow BG, King BA. 2015. Tofacitinib citrate for the treatment of vitiligo. JAMA Dermatol 151:101110–13
    [Google Scholar]
  86. 86. 
    Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G et al. 2016. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J. Am. Dermatol. 74:2370–71
    [Google Scholar]
  87. 87. 
    Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H et al. 2017. Treatment of vitiligo with the topical Janus kinase inhibitor ruxolitinib. J. Am. Dermatol. 76:61054–60.e1
    [Google Scholar]
  88. 88. 
    Rosmarin D, Pandya A, Lebwohl M, Grimes P, Hamzavi I et al. 2019. Efficacy and safety of ruxolitinib cream for the treatment of vitiligo: results of a 24-week randomized, double-blind, dose-ranging, vehicle-controlled study. Presented at 24th World Congress of Dermatology, Milan
  89. 89. 
    Liu LY, Strassner JP, Refat MA, Harris JE, King BA 2017. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure. J. Am. Dermatol. 77:4675–82.e1
    [Google Scholar]
  90. 90. 
    McKesey J, Pandya AG. 2019. A pilot study of 2% tofacitinib cream with narrowband ultraviolet B for the treatment of facial vitiligo. J. Am. Acad. Dermatol. 81:2646–48
    [Google Scholar]
  91. 91. 
    Wang H, Brown J, Gao S, Liang S, Jotwani R et al. 2013. The role of JAK-3 in regulating TLR-mediated inflammatory cytokine production in innate immune cells. J. Immunol. 191:31164–74
    [Google Scholar]
  92. 92. 
    Gadina M. 2013. Janus kinases: an ideal target for the treatment of autoimmune diseases. J. Investig. Dermatol. Symp. Proc. 16:1S70–72
    [Google Scholar]
  93. 93. 
    Sohn SJ, Barrett K, Van Abbema A, Chang C, Kohli PB et al. 2013. A restricted role for TYK2 catalytic activity in human cytokine responses revealed by novel TYK2-selective inhibitors. J. Immunol. 191:52205–16
    [Google Scholar]
  94. 94. 
    Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF et al. 2018. Dual inhibition of TYK2 and JAK1 for the treatment of autoimmune diseases: discovery of ((S)‐2,2-difluorocyclopropyl)((1R,5S)‐3-(2-((1-methyl‐1H‐pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J. Med. Chem. 61:198597–612
    [Google Scholar]
  95. 95. 
    Jacquemin C, Rambert J, Guillet S, Thiolat D, Boukhedouni N et al. 2017. Heat shock protein 70 potentiates interferon alpha production by plasmacytoid dendritic cells: relevance for cutaneous lupus and vitiligo pathogenesis. Br. J. Dermatol. 177:51367–75
    [Google Scholar]
  96. 96. 
    Nirula A, Nilsen J, Klekotka P, Kricorian G, Erondu N et al. 2016. Effect of IL-17 receptor A blockade with brodalumab in inflammatory diseases. Rheumatology 55:Suppl. 2ii43–55
    [Google Scholar]
  97. 97. 
    Kavanaugh A, Puig L, Gottlieb AB, Ritchlin C, You Y et al. 2016. Efficacy and safety of ustekinumab in psoriatic arthritis patients with peripheral arthritis and physician-reported spondylitis: post-hoc analyses from two phase III, multicentre, double-blind, placebo-controlled studies (PSUMMIT-1/PSUMMIT-2). Ann. Rheum. Dis. 75:111984–88
    [Google Scholar]
  98. 98. 
    Lebwohl M, Strober B, Menter A, Gordon K, Weglowska J et al. 2015. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N. Engl. J. Med. 373:141318–28
    [Google Scholar]
  99. 99. 
    Bassiouny DA, Shaker O. 2010. Role of interleukin-17 in the pathogenesis of vitiligo. Clin. Exp. Dermatol. 36:3292–97
    [Google Scholar]
  100. 100. 
    Singh RK, Lee KM, Vujkovic-Cvijin I, Ucmak D, Farahnik B et al. 2016. The role of IL-17 in vitiligo: a review. Autoimmun. Rev. 15:4397–404
    [Google Scholar]
  101. 101. 
    Speeckaert R, Mylle S, Geel N 2019. IL‐17A is not a treatment target in progressive vitiligo. Pigment Cell Melanoma Res 31:2330–37
    [Google Scholar]
  102. 102. 
    AlGhamdi KM, Khurrum H, Taieb A, Ezzedine K 2017. Treatment of generalized vitiligo with anti-TNF-α agents. J. Drugs Dermatol. 11:4534–39
    [Google Scholar]
  103. 103. 
    Bae JM, Kim M, Lee HH, Kim K-J, Shin H et al. 2018. Increased risk of vitiligo following anti-tumor necrosis factor therapy: a 10-year population-based cohort study. J. Investig. Dermatol. 138:4768–74
    [Google Scholar]
  104. 104. 
    Méry-Bossard L, Bagny K, Chaby G, Khemis A, Maccari F et al. 2016. New-onset vitiligo and progression of pre-existing vitiligo during treatment with biological agents in chronic inflammatory diseases. J. Eur. Acad. Dermatol. Venerol. 31:1181–86
    [Google Scholar]
  105. 105. 
    Toussirot É, Aubin F. 2016. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview. RMD Open 2:2e000239–12
    [Google Scholar]
  106. 106. 
    Webb KC, Tung R, Winterfield LS, Gottlieb AB, Eby JM et al. 2015. Tumour necrosis factor-α inhibition can stabilize disease in progressive vitiligo. Br. J. Dermatol. 173:3641–50
    [Google Scholar]
  107. 107. 
    Cheuk S, Schlums H, Sérézal IG, Martini E, Chiang SC et al. 2017. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity 46:2287–300
    [Google Scholar]
  108. 108. 
    Palucka AK, Blanck J-P, Bennett L, Pascual V, Banchereau J 2005. Cross-regulation of TNF and IFN-α in autoimmune diseases. PNAS 102:3372–77
    [Google Scholar]
  109. 109. 
    Mueller SN, Gebhardt T, Carbone FR, Heath WR 2013. Memory T cell subsets, migration patterns, and tissue residence. Annu. Rev. Immunol. 31:1137–61
    [Google Scholar]
  110. 110. 
    Steinbach K, Vincenti I, Merkler D 2018. Resident-memory T cells in tissue-restricted immune responses: for better or worse. ? Front. Immunol. 9:2827
    [Google Scholar]
  111. 111. 
    Jiang X, Clark RA, Liu L, Wagers AJ, Fuhlbrigge RC, Kupper TS 2012. Skin infection generates non-migratory memory CD8+ TRM cells providing global skin immunity. Nature 483:7388227–31
    [Google Scholar]
  112. 112. 
    Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D 2014. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346:620598–101
    [Google Scholar]
  113. 113. 
    Ariotti S, Hogenbirk MA, Dijkgraaf FE, Visser LL, Hoekstra ME et al. 2014. Skin-resident memory CD8+ T cells trigger a state of tissue-wide pathogen alert. Science 346:6205101–5
    [Google Scholar]
  114. 114. 
    Zhu J, Peng T, Johnston C, Phasouk K, Kask AS et al. 2014. Immune surveillance by CD8αα+ skin-resident T cells in human herpes virus infection. Nature 497:7450494–97
    [Google Scholar]
  115. 115. 
    Dijkgraaf FE, Matos TR, Hoogenboezem M, Toebes M, Vredevoogd DW et al. 2019. Tissue patrol by resident memory CD8+ T cells in human skin. Nat. Immunol. 20:6756–64
    [Google Scholar]
  116. 116. 
    Mueller SN, Mackay LK. 2015. Tissue-resident memory T cells: local specialists in immune defence. Nat. Rev. Immunol. 16:279–89
    [Google Scholar]
  117. 117. 
    Topham DJ, Reilly EC. 2018. Tissue-resident memory CD8+ T cells: from phenotype to function. Front. Immunol. 9:515
    [Google Scholar]
  118. 118. 
    Szabo PA, Levitin HM, Miron M, Snyder ME, Senda T et al. 2019. A single-cell reference map for human blood and tissue T cell activation reveals functional states in health and disease. bioRxiv 555557. https://doi.org/10.1101/555557
    [Crossref]
  119. 119. 
    Pan Y, Tian T, Park CO, Lofftus SY, Mei S et al. 2017. Survival of tissue-resident memory T cells requires exogenous lipid uptake and metabolism. Nature 543:7644252–56
    [Google Scholar]
  120. 120. 
    Pan Y, Kupper TS. 2018. Metabolic reprogramming and longevity of tissue-resident memory T cells. Front. Immunol. 9:745–47
    [Google Scholar]
  121. 121. 
    Mackay LK, Rahimpour A, Ma JZ, Collins N, Stock AT et al. 2013. The developmental pathway for CD103+CD8+ tissue-resident memory T cells of skin. Nat. Immunol. 14:121294–301
    [Google Scholar]
  122. 122. 
    Miragaia RJ, Gomes T, Chomka A, Jardine L, Riedel A et al. 2019. Single-cell transcriptomics of regulatory T cells reveals trajectories of tissue adaptation. Immunity 50:2493–97
    [Google Scholar]
  123. 123. 
    Richmond JM, Strassner JP, Rashighi M, Agarwal P, Garg M et al. 2019. Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo. J. Investig. Dermatol. 139:4769–78
    [Google Scholar]
  124. 124. 
    Richmond JM, Strassner JP, Zapata L Jr., Garg M, Riding RL et al. 2018. Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo. Sci. Transl. Med. 10:1–10
    [Google Scholar]
  125. 125. 
    Mackay LK, Stock AT, Ma JZ, Jones CM, Kent SJ et al. 2012. Long-lived epithelial immunity by tissue-resident memory T (TRM) cells in the absence of persisting local antigen presentation. PNAS 109:7037–42
    [Google Scholar]
  126. 126. 
    Schenkel JM, Fraser KA, Vezys V, Masopust D 2013. Sensing and alarm function of resident memory CD8+ T cells. Nat. Immunol. 14:5509–13
    [Google Scholar]
  127. 127. 
    Seidel JA, Vukmanovic-Stejic M, Muller-Durovic B, Patel N, Fuentes-Duculan J et al. 2018. Skin resident memory CD8+ T cells are phenotypically and functionally distinct from circulating populations and lack immediate cytotoxic function. Clin. Exp. Immunol. 194:179–92
    [Google Scholar]
  128. 128. 
    McMaster SR, Wilson JJ, Wang H, Kohlmeier JE 2015. Airway-resident memory CD8 T cells provide antigen-specific protection against respiratory virus challenge through rapid IFN-γ production. J. Immunol. 195:1203–9
    [Google Scholar]
  129. 129. 
    Malik BT, Byrne KT, Vella JL, Zhang P, Shabaneh TB et al. 2017. Resident memory T cells in the skin mediate durable immunity to melanoma. Sci. Immunol 2:10eaam6346
    [Google Scholar]
  130. 130. 
    Park SL, Buzzai A, Rautela J, Hor JL, Hochheiser K et al. 2019. Tissue-resident memory CD8+ T cells promote melanoma-immune equilibrium in skin. Nature 565:7739366–71 Correction. 2019. Nature 566(7745):E10
    [Google Scholar]
  131. 131. 
    Adachi T, Kobayashi T, Sugihara E, Yamada T, Ikuta K et al. 2015. Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell homeostasis and lymphoma. Nat. Med. 21:111272–79
    [Google Scholar]
  132. 132. 
    Baumann NS, Torti N, Welten SPM, Barnstorf I, Borsa M et al. 2018. Tissue maintenance of CMV-specific inflationary memory T cells by IL-15. PLOS Pathog 14:4e1006993–23
    [Google Scholar]
  133. 133. 
    Budagian V, Bulanova E, Paus R, Bulfone-Paus S 2006. IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev 17:4259–80
    [Google Scholar]
  134. 134. 
    Vamosi G, Bodnar A, Vereb G, Jenei A, Goldman CK et al. 2004. IL-2 and IL-15 receptor α-subunits are coexpressed in a supramolecular receptor cluster in lipid rafts of T cells. PNAS 101:11082–87
    [Google Scholar]
  135. 135. 
    Alves NL. 2003. IL-15 induces antigen-independent expansion and differentiation of human naive CD8+ T cells in vitro. Blood 102:72541–46
    [Google Scholar]
  136. 136. 
    Lahl K, Loddenkemper C, Drouin C, Freyer J, Arnason J et al. 2007. Selective depletion of Foxp3+ regulatory T cells induces a scurfy-like disease. J. Exp. Med. 204:157–63
    [Google Scholar]
  137. 137. 
    Chatterjee S, Eby JM, Al-Khami AA, Soloshchenko M, Kang H-K et al. 2014. A quantitative increase in regulatory T cells controls development of vitiligo. J. Investig. Dermatol. 134:51285–94
    [Google Scholar]
  138. 138. 
    Eby JM, Kang H-K, Tully ST, Bindeman WE, Peiffer DS et al. 2015. CCL22 to activate Treg migration and suppress depigmentation in vitiligo. J. Investig. Dermatol. 135:61574–80
    [Google Scholar]
  139. 139. 
    Miao X, Xu R, Fan Bin, Chen J, Li X et al. 2018. PD-L1 reverses depigmentation in Pmel-1 vitiligo mice by increasing the abundance of Tregs in the skin. Sci. Rep. 8:11605
    [Google Scholar]
  140. 140. 
    Lili Y, Yi W, Ji Y, Yue S, Weimin S, Ming L 2012. Global activation of CD8+ cytotoxic T lymphocytes correlates with an impairment in regulatory T cells in patients with generalized vitiligo. PLOS ONE 7:5e37513–10
    [Google Scholar]
  141. 141. 
    Klarquist J, Denman CJ, Hernandez C, Wainwright DJ, Strickland FM et al. 2010. Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res 23:2276–86
    [Google Scholar]
  142. 142. 
    Ben Ahmed M, Zaraa I, Rekik R, Elbeldi-Ferchiou A, Kourda N et al. 2011. Functional defects of peripheral regulatory T lymphocytes in patients with progressive vitiligo. Pigment Cell Melanoma Res 25:199–109
    [Google Scholar]
  143. 143. 
    Terras S, Gambichler T, Moritz RK, Altmeyer P, Lambert J 2014. Immunohistochemical analysis of FOXP3+ regulatory T cells in healthy human skin and autoimmune dermatoses. Int. J. Dermatol. 53:294–99
    [Google Scholar]
  144. 144. 
    Abdallah M, Lotfi R, Othman W, Galal R 2014. Assessment of tissue FoxP3+, CD4+ and CD8+ T-cells in active and stable nonsegmental vitiligo. Int. J. Dermatol. 53:940–46
    [Google Scholar]
  145. 145. 
    Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M et al. 2014. Detection of self-reactive CD8+ T cells with an anergic phenotype in healthy individuals. Science 346:62161536–40
    [Google Scholar]
  146. 146. 
    Hassin D, Garber OG, Meiraz A, Schiffenbauer YS, Berke G 2011. Cytotoxic T lymphocyte perforin and Fas ligand working in concert even when Fas ligand lytic action is still not detectable. Immunology 133:2190–96
    [Google Scholar]
  147. 147. 
    Leisegang M, Kammertoens T, Uckert W, Blankenstein T 2016. Targeting human melanoma neoantigens by T cell receptor gene therapy. J. Clin. Investig. 126:854–58
    [Google Scholar]
  148. 148. 
    Bethune MT, Joglekar AV. 2017. Personalized T cell-mediated cancer immunotherapy: progress and challenges. Curr. Opin. Biotechnol. 48:142–52
    [Google Scholar]
  149. 149. 
    James EA, Pietropaolo M, Mamula MJ 2018. Immune recognition of β-cells: neoepitopes as key players in the loss of tolerance. Diabetes 67:61035–42
    [Google Scholar]
  150. 150. 
    Wiles TA, Delong T, Baker RL, Bradley B, Barbour G et al. 2017. An insulin-IAPP hybrid peptide is an endogenous antigen for CD4 T cells in the non-obese diabetic mouse. J. Autoimm. 78:11–18
    [Google Scholar]
  151. 151. 
    Babon JAB, DeNicola ME, Blodgett DM, Crèvecoeur I, Buttrick TS et al. 2016. Analysis of self-antigen specificity of islet-infiltrating T cells from human donors with type 1 diabetes. Nat. Med. 22:121482–87
    [Google Scholar]
  152. 152. 
    Boissy RE, Liu Y-Y, Medrano EE, Nordlund JJ 1991. Structural aberration of the rough endoplasmic reticulum and melanosome compartmentalization in long-term cultures of melanocytes from vitiligo patients. J. Investig. Dermatol. 97:3395–404
    [Google Scholar]
  153. 153. 
    Schallreuter KU, Salem MAEL, Holtz S, Panske A 2013. Basic evidence for epidermal H2O2/ONOO mediated oxidation/nitration in segmental vitiligo is supported by repigmentation of skin and eyelashes after reduction of epidermal H2O2 with topical NB-UVB-activated pseudocatalase PC-KUS. FASEB J 27:83113–22
    [Google Scholar]
  154. 154. 
    Richmond JM, Frisoli ML, Harris JE 2013. Innate immune mechanisms in vitiligo: danger from within. Curr. Opin. Immunol. 25:6676–82
    [Google Scholar]
  155. 155. 
    Yu R, Broady R, Huang Y, Wang Y, Yu J et al. 2012. Transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin. PLOS ONE 7:12e51040–12
    [Google Scholar]
  156. 156. 
    Oliver EA, Schwartz L, Warren LH 1939. Occupational leukoderma. JAMA 113:927–28
    [Google Scholar]
  157. 157. 
    Mosher DB, Parrish JA, Fitzpatrick TB 1977. Monobenzylether of hydroquinone. Br. J. Dermatol. 97:669–79
    [Google Scholar]
  158. 158. 
    Ghosh S, Mukhopadhyay S. 2009. Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country. Br. J. Dermatol. 160:140–47
    [Google Scholar]
  159. 159. 
    Harris JE. 2017. Chemical-induced vitiligo. Dermatol. Clin. 35:2151–61
    [Google Scholar]
  160. 159a. 
    Nishigori C, Aoyama Y, Ito A, Suzuki K, Suzuki Tet al 2015. Guide for medical professionals (i.e., dermatologists) for the management of rhododendrol-induced leukoderma. J. Dermatol 42:113–28
    [Google Scholar]
  161. 159b. 
    Tokura Y, Fujiyama T, Ikeya S, Tatsuno K, Masahiro Aet al 2015. Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma. J. Dermatol. Sci 77:146–49
    [Google Scholar]
  162. 160. 
    van den Boorn JG, Picavet DI, van Swieten PF, van Veen HA, Konijnenberg D et al. 2011. Skin-depigmenting agent monobenzone induces potent T-cell autoimmunity toward pigmented cells by tyrosinase haptenation and melanosome autophagy. J. Investig. Dermatol. 131:61240–51
    [Google Scholar]
  163. 161. 
    Yang F, Sarangarajan R, Le Poole IC, Boissy RE, Medrano EE 2000. The cytotoxicity and apoptosis induced by 4-tertiary butylphenol in human melanocytes are independent of tyrosinase activity. J. Investig. Dermatol. 114:1157–64
    [Google Scholar]
  164. 162. 
    Lancaster GI, Febbraio MA. 2005. Exosome-dependent trafficking of HSP70. J. Biol. Chem. 280:2423349–55
    [Google Scholar]
  165. 163. 
    Mosenson JA, Flood K, Klarquist J, Eby JM, Koshoffer A et al. 2014. Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress. Pigment Cell Melanoma Res 27:2209–20
    [Google Scholar]
  166. 164. 
    Levandowski CB, Mailloux CM, Ferrara TM, Gowan K, Ben S et al. 2013. NLRP1 haplotypes associated with vitiligo and autoimmunity increase interleukin-1β processing via the NLRP1 inflammasome. PNAS 110:82952–56
    [Google Scholar]
  167. 165. 
    Kroll TM, Bommiasamy H, Boissy RE, Hernandez C, Nickoloff BJ et al. 2005. 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing: relevance to vitiligo. J. Investig. Dermatol. 124:4798–806
    [Google Scholar]
  168. 166. 
    van den Boorn JG, Jakobs C, Hagen C, Renn M, Luiten RM et al. 2016. Inflammasome-dependent induction of adaptive NK cell memory. Immunity 44:61406–21
    [Google Scholar]
  169. 167. 
    Denman CJ, McCracken J, Hariharan V, Klarquist J, Oyarbide-Valencia K et al. 2008. HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo. J. Investig. Dermatol. 128:82041–48
    [Google Scholar]
  170. 168. 
    Mosenson JA, Zloza A, Nieland JD, Garret-Mayer E, Eby JM et al. 2013. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci. Transl. Med. 5:174174ra28
    [Google Scholar]
  171. 169. 
    Henning SW, Fernandez MF, Mahon J, Duff R, Azarafrooz F et al. 2018. HSP70iQ435A-encoding DNA repigments vitiligo lesions in Sinclair swine. J. Investig. Dermatol. 138:122531–39
    [Google Scholar]
  172. 170. 
    Wang CQF, Cruz-Inigo AE, Fuentes-Duculan J, Moussai D, Gulati N et al. 2011. Th17 cells and activated dendritic cells are increased in vitiligo lesions. PLOS ONE 6:4e18907–11
    [Google Scholar]
  173. 171. 
    Tulic MK, Cavazza E, Cheli Y, Jacquel A, Luci C et al. 2019. Innate lymphocyte-induced CXCR3B-mediated melanocyte apoptosis is a potential initiator of T-cell autoreactivity in vitiligo. Nat. Commun. 10:12178
    [Google Scholar]
  174. 172. 
    Marie J, Kovacs D, Pain C, Jouary T, Cota C et al. 2014. Inflammasome activation and vitiligo/nonsegmental vitiligo progression. Br. J. Dermatol. 170:4816–23
    [Google Scholar]
  175. 173. 
    Kosche C, Mohindra N, Choi JN 2018. Vitiligo in a patient undergoing nivolumab treatment for non-small cell lung cancer. JAAD Case Rep 4:101042–44
    [Google Scholar]
  176. 174. 
    Hua C, Boussemart L, Mateus C, Routier E, Boutros C et al. 2016. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol 152:145–47
    [Google Scholar]
  177. 175. 
    Fecher LA, Agarwala SS, Hodi FS, Weber JS 2013. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist 18:6733–43
    [Google Scholar]
  178. 176. 
    Barbulescu CC, Goldstein NB, Roop DR, Norris DA, Birlea SA 2020. Harnessing the power of regenerative therapy for vitiligo and alopecia areata. J. Investig. Dermatol. 140:129–37
    [Google Scholar]
  179. 177. 
    Nishimura EK. 2011. Melanocyte stem cells: a melanocyte reservoir in hair follicles for hair and skin pigmentation. Pigment Cell Melanoma Res 24:3401–10
    [Google Scholar]
  180. 178. 
    Joshi SS, Tandukar B, Pan L, Huang JM, Livak F et al. 2019. CD34 defines melanocyte stem cell subpopulations with distinct regenerative properties. PLOS Genet 15:4e1008034–25
    [Google Scholar]
  181. 179. 
    Mort RL, Jackson IJ, Patton EE 2015. The melanocyte lineage in development and disease. Development 142(4):620–32. Erratum. 2015. Development 142(7):1387
  182. 180. 
    Paus R, Nickoloff B, Ito T 2005. A “hairy” privilege. Trends Immunol 26:132–40
    [Google Scholar]
  183. 181. 
    Harrist TJ, Ruiter DJ, Mihm MJ, Bhan AK 1983. Distribution of major histocompatibility antigens in normal skin. Br. J. Dermatol. 109:623–33
    [Google Scholar]
  184. 182. 
    Christoph T, Muller-Rover S, Audring H, Tobin DJ, Hermes B et al. 2000. The human hair follicle immune system: cellular composition and immune privilege. Br. J. Dermatol. 142:862–73
    [Google Scholar]
  185. 183. 
    Ito T, Ito N, Saatoff M, Hashizume H, Fukamizu H et al. 2008. Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. J. Investig. Dermatol. 128:51196–206
    [Google Scholar]
  186. 184. 
    Ali N, Zirak B, Rodriguez RS, Pauli ML, Truong H-A et al. 2017. Regulatory T cells in skin facilitate epithelial stem cell differentiation. Cell 169:61119–1123.e11
    [Google Scholar]
  187. 185. 
    Chou WC, Takeo M, Rabbani P, Hu H, Lee W et al. 2013. Direct migration of follicular melanocyte stem cells to the epidermis after wounding or UVB irradiation is dependent on Mc1r signaling. Nat. Med. 19:924–31
    [Google Scholar]
  188. 186. 
    Moon H, Donahue LR, Choi E, Scumpia PO, Lowry WE et al. 2017. Melanocyte stem cell activation and translocation initiate cutaneous melanoma in response to UV exposure. Stem Cell 21:5665–66
    [Google Scholar]
  189. 187. 
    Horikawa T, Norris DA, Yohn JJ, Zekman T, Travers JB, Morelli JG 1995. Melanocyte mitogens induce both melanocyte chemokinesis and chemotaxis. J. Investig. Dermatol. 104:2256–59
    [Google Scholar]
  190. 188. 
    Yamada T, Hasegawa S, Inoue Y, Date Y, Yamamoto N et al. 2013. Wnt/β-catenin and kit signaling sequentially regulate melanocyte stem cell differentiation in UVB-induced epidermal pigmentation. J. Investig. Dermatol. 133:2753–62
    [Google Scholar]
  191. 189. 
    Tagashira H, Miyamoto A, Kitamura S-I, Tsubata M, Yamaguchi K et al. 2015. UVB stimulates the expression of endothelin B receptor in human melanocytes via a sequential activation of the p38/MSK1/CREB/MITF pathway which can be interrupted by a French maritime pine bark extract through a direct inactivation of MSK1. PLOS ONE 10:6e0128678–17
    [Google Scholar]
  192. 190. 
    Hachiya A, Kobayashi A, Yoshida Y, Kitahara T, Takema Y, Imokawa G 2010. Biphasic expression of two paracrine melanogenic cytokines, stem cell factor and endothelin-1, in ultraviolet B-induced human melanogenesis. Am. J. Pathol. 165:62099–109
    [Google Scholar]
  193. 191. 
    Takeo M, Lee W, Rabbani P, Sun Q, Hu H et al. 2016. EdnrB governs regenerative response of melanocyte stem cells by crosstalk with Wnt signaling. Cell Rep 15:61291–302
    [Google Scholar]
  194. 192. 
    Sun Q, Rabbani P, Takeo M, Lee S-H, Lim CH et al. 2018. Dissecting Wnt signaling for melanocyte regulation during wound healing. J. Investig. Dermatol. 138:71591–600
    [Google Scholar]
  195. 193. 
    Grimes PE, Hamzavi I, Lebwohl M, Ortonne J-P, Lim HW 2013. The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo. JAMA Dermatol 149:168–73
    [Google Scholar]
  196. 194. 
    Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M et al. 2015. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo. JAMA Dermatol 151:142–49
    [Google Scholar]
  197. 195. 
    Qiu W, Yang K, Lei M, Yan H, Tang H et al. 2015. SCF/c-kit signaling is required in 12-O-tetradecanoylphorbol-13-acetate-induced migration and differentiation of hair follicle melanocytes for epidermal pigmentation. Cell Tissue Res 360:2333–46
    [Google Scholar]
  198. 196. 
    Qiu W, Tang H, Guo H, Lei M, Yan H et al. 2016. 12-O-tetradecanoylphorbol-13-acetate activates hair follicle melanocytes for hair pigmentation via Wnt/β-catenin signaling. Cell Tissue Res 366:2329–40
    [Google Scholar]
  199. 197. 
    Regazzetti C, Joly F, Marty C, Rivier M, Mehul B et al. 2015. Transcriptional analysis of vitiligo skin reveals the alteration of WNT pathway: a promising target for repigmenting vitiligo patients. J. Investig. Dermatol. 135:123105–14
    [Google Scholar]
/content/journals/10.1146/annurev-immunol-100919-023531
Loading
/content/journals/10.1146/annurev-immunol-100919-023531
Loading

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error