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Vitiligo pp 205-223 | Cite as

Animal Models

  • Gisela F. ErfEmail author
  • I. Caroline Le Poole
Chapter
  • 271 Downloads

Abstract

Vitiligo is a non-communicable, multifactorial pigmentation disorder. Autoimmunity has been identified as a major etiological factor in the postnatal loss of epidermal melanocytes in the skin of vitiligo patients. As with other tissue-specific autoimmune diseases, genetic predisposition to vitiligo development may be manifested in altered responsiveness of tissue cells and immune system components to endogenous and exogenous environmental factors, leading to immunorecognition and immune system-mediated loss of melanocytes. To understand the etiology and pathogenic mechanisms driving disease onset and progression, and to develop effective treatment and prevention strategies for autoimmune vitiligo, appropriate animal models are required. In this context, experimental animal models that naturally develop vitiligo would more closely reflect the complex nature of the disorder in humans than experimental models where the autoimmune disease was induced. Animal models with truly naturally occurring autoimmune disease are rare. However, for autoimmune vitiligo, the Smyth line of chicken was established as a highly relevant, spontaneous model for both basic and translational research, as it displays the entire spectrum of clinical and biological manifestations of autoimmune vitiligo in humans. While there is no natural vitiligo mouse model, induction of vitiligo in mice by generation of melanocyte-specific immune responses proved to be an invaluable approach to dissect cellular and molecular mechanisms involved in the autoimmune depigmentation and repigmentation processes. Together, research using the natural and induced animal models will provide the critical knowledge needed to understand, treat, and prevent autoimmune vitiligo.

References

  1. 1.
    Harris JE. Cellular stress and innate inflammation in organ-specific autoimmunity: lessons learned from vitiligo. Immunol Rev. 2016;269:11–25.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Le Poole IC, Luiten RM. Autoimmune etiology of generalized vitiligo. In: Nickoloff BJ, Nestle FO, editors. Current directions in autoimmunity: dermatologic immunity, vol. 10. Basel: Karger; 2008. p. 227–43.Google Scholar
  3. 3.
    Le Poole IC, Das PK, van den Wijngaard RMJGJ, et al. Review of the etiopathomechanism of vitiligo: a convergence theory. Exp Dermatol. 1993;2:145–53.PubMedGoogle Scholar
  4. 4.
    Nordlund JJ, Lerner AB. Vitiligo-it is important. Arch Dermatol. 1982;118:5–8.PubMedGoogle Scholar
  5. 5.
    Picardo M, Dell’Anna ML, Ezzedine K, et al. Vitiligo. Nat Rev Dis Primers. 2015;1:15011.PubMedGoogle Scholar
  6. 6.
    Rezaei N, Gavalas NG, Weetman AP, et al. Autoimmunity as an aetiological factor in vitiligo. J Eur Acad Dermatol Venereol. 2007;21:865–76.PubMedGoogle Scholar
  7. 7.
    Schallreuter KU, Wood JM, Berger J. Low catalase levels in the epidermis of patients with vitiligo. J Invest Dermatol. 1991;97:1081–5.PubMedGoogle Scholar
  8. 8.
    Spritz RA. The genetics of generalized vitiligo and associated autoimmune diseases. Pigment Cell Res. 2007;20:271–8.PubMedGoogle Scholar
  9. 9.
    Erf GF. Autoimmune diseases of poultry. In: Schat KA, Kaspers B, Kaiser P, editors. Avian immunology. London: Elsevier; 2014.Google Scholar
  10. 10.
    Krishnamoorthy G, Holz A, Wekerle H. Experimental models of spontaneous autoimmune disease in the central nervous system. J Mol Med. 2007;85:1161–73.PubMedGoogle Scholar
  11. 11.
    National Institutes of Health Autoimmune Diseases Coordinating Committee. Autoimmune diseases research plan. In: Progress in autoimmune disease. Bethesda, MD: Research NIH; 2005.Google Scholar
  12. 12.
    Wick G, Andersson L, Hala K, et al. Avian models with spontaneous autoimmune diseases. Adv Immunol. 2006;92:71–117.PubMedPubMedCentralGoogle Scholar
  13. 13.
    Boissy RE, Lamoreux ML. Animal models of an acquired pigmentary disorder-vitiligo. Prog Clin Biol Res. 1988;256:207–18.PubMedGoogle Scholar
  14. 14.
    Erf GF (2010) Animal models. In: Vitiligo, Picardo M A. Taieb, 205-218 Springer, Berlin.Google Scholar
  15. 15.
    Essien KI, Harris JE. Animal models of vitiligo: matching the model to the question. Dermatol Sinica. 2014;32:240–7.Google Scholar
  16. 16.
    Smyth JR Jr. The Smyth chicken: a model for autoimmune amelanosis. Poult Biol. 1989;2:1–19.Google Scholar
  17. 17.
    Cerundolo R, De Caprariis D, Esposito L, et al. Vitiligo in two water buffaloes: histological, histochemical, and ultrastructural investigations. Pigment Cell Res. 1993;6:23–8.PubMedGoogle Scholar
  18. 18.
    Singh V, Motiani R, Singh A, et al. Water Buffalo (Bubalus bubalis) as a spontaneous animal model of vitiligo. Pigment Cell Melanoma Res. 2016;29:465.  https://doi.org/10.1111/pcmr.12485.CrossRefPubMedGoogle Scholar
  19. 19.
    Berkelhammer J, Ensign BM, Hook RR, et al. Growth and spontaneous regression of swine melanoma: relationship of in vitro leukocyte reactivity. J Natl Cancer Inst. 1982;68:461–8.PubMedGoogle Scholar
  20. 20.
    Misfeldt ML, Grimm DR. Sinclair miniature swine: an animal model of human melanoma. Vet Immunol Immunopathol. 1994;43:167–75.PubMedGoogle Scholar
  21. 21.
    Richerson JT, Burns RP, Misfeldt ML. Association of uveal melanocyte destruction in melanoma-bearing swine with large granular lymphocyte cells. Invest Ophthalmol Vis Sci. 1989;30:2455–60.PubMedGoogle Scholar
  22. 22.
    Gebhart W, Niebauer G. Connections between pigment loss and melanogenesis in gray horses of the Lipizzaner breed. Yale J Biol Med. 1977;50:45.Google Scholar
  23. 23.
    Naughton GK, Mahaffey M, Bystryn J-C. Antibodies to surface antigens of pigmented cells in animals with vitiligo. Proc Soc Exp Biol Med. 1986;181:423–6.PubMedGoogle Scholar
  24. 24.
    Bowers RR, Harmon J, Prescott S, et al. Fowl model for vitiligo: genetic regulation on the fate of the melanocytes. Pigment Cell Res Suppl. 1992;2:242–8.Google Scholar
  25. 25.
    Bowers RR, Lujan J, Biboso A, et al. Premature avian melanocyte death due to low antioxidant levels of protection: fowl model for vitiligo. Pigment Cell Res. 1994;7:409–18.PubMedGoogle Scholar
  26. 26.
    Bowers RR, Nguyen B, Buckner S, et al. Role of anti-oxidants in the survival of normal and vitiliginous avian melanocytes. Cell Mol Biol. 1999;45:1065–74.PubMedGoogle Scholar
  27. 27.
    Boissy RE, Moellmann GE, Lerner AB. Morphology of melanocytes in hair bulbs and eyes of vitiligo mice. Am J Pathol. 1987;127:380–8.PubMedPubMedCentralGoogle Scholar
  28. 28.
    Lamoreux ML, Boissy RE, Womack JE, et al. The vit gene maps to the mi (microphthalmia) locus of the laboratory mouse. J Hered. 1992;83:435–9.PubMedGoogle Scholar
  29. 29.
    Lerner AB, Shiohara T, Boissy RE, et al. A possible mouse model for vitiligo. J Invest Dermatol. 1986;87:299–304.PubMedGoogle Scholar
  30. 30.
    Tripathi RK, Flanders DJ, Young TL, et al. Microphthalmia-associated transcription factor (MITF) locus lacks linkage to human vitiligo or osteoporosis: an evaluation. Pigment Cell Res. 1999;12:187–92.PubMedGoogle Scholar
  31. 31.
    Erf GF, Ramachandran IR. The growing feather as a dermal test-site: comparison of leukocyte profiles during the response to Mycobacterium butyricum in growing feathers, wattles, and wing webs. Poult Sci. 2016;95:2011–122.PubMedPubMedCentralGoogle Scholar
  32. 32.
    Smyth JR Jr, McNeil M. Alopecia areata and universalis in the Smyth chicken model for spontaneous autoimmune vitiligo. J Invest Dermatol Symp Proc. 1999;4:211–5.Google Scholar
  33. 33.
    Smyth JR Jr, Boissy RE, Fite KV. The DAM chicken: a model for spontaneous postnatal cutaneous and ocular amelanosis. J Hered. 1981;72:150–6.PubMedGoogle Scholar
  34. 34.
    Kerje S, Ek W, Asahlquist A-S, Ekwall O, Erf G, Carlborg Ö, Andersson L, Kämpe O. Genetic mapping of loci underlying vitiligo in the Smyth line chicken model. Pigment Cell Melanoma Res. 2011;24:831.Google Scholar
  35. 35.
    Jang H-M, Erf GF, Rowland KC, et al. Genome resequencing and bioinformatics analysis of SNP containing candidate genes in the autoimmune vitiligo Smyth line chicken model. BMC Genomics. 2014;15:707.PubMedPubMedCentralGoogle Scholar
  36. 36.
    Sreekumar GP, Smyth JR Jr, Ponce de Leon FA. Molecular characterization of the Smyth chicken sublines and their parental controls by RFLP and DNA fingerprint analysis. Poult Sci. 2001;80:1–5.PubMedGoogle Scholar
  37. 37.
    Sreekumar GP, Erf GF, Smyth JR Jr. 5-Azacytidine treatment induces autoimmune vitiligo in the parental control strains of the Smyth line chicken model for autoimmune vitiligo. Clin Immunol Immunopathol. 1996;81:136–44.PubMedGoogle Scholar
  38. 38.
    Erf GF, Smyth JR Jr. Alterations in blood leukocyte populations in Smyth line chickens with autoimmune vitiligo. Poult Sci. 1996;75:351–6.PubMedGoogle Scholar
  39. 39.
    Erf GF, Trejo-Skalli AV, Smyth JRJ. T cells in regenerating feathers of Smyth line chickens with vitiligo. Clin Immunol Immunopathol. 1995;76:120–6.PubMedGoogle Scholar
  40. 40.
    Shresta S, Smyth JR Jr, Erf GF. Profiles of pulp infiltrating lymphocytes at various times throughout feather regeneration in Smyth line chickens with vitiligo. Autoimmunity. 1997;25:193–201.PubMedGoogle Scholar
  41. 41.
    Wang X, Erf GF. Apoptosis in feathers of Smyth line chickens with autoimmune vitiligo. J Autoimmun. 2004;22:21–30.PubMedGoogle Scholar
  42. 42.
    Falcon DM, Dienglewicz RL, Erf GF. Monitoring of leukocyte infiltration responses to melanocytes injected into growing feathers of Smyth line chickens with autoimmune vitiligo. Pigment Cell Melanoma Res. 2015;28:627.Google Scholar
  43. 43.
    Wang X, Erf GF. Melanocyte-specific cell mediated immune response in vitiliginous Smyth line chickens. J Autoimmun. 2003;21:149–60.PubMedGoogle Scholar
  44. 44.
    Shi F, Erf GF. IFN-gamma, IL-21 and IL-10 co-expression in evolving autoimmune vitiligo lesions of Smyth line chickens. J Invest Dermatol. 2012;132:642–9.PubMedGoogle Scholar
  45. 45.
    Leonard WJ, Zeng R, Spolski R. Interleukin 21: a chemokine/cytokine receptor system that has come of age. J Leukoc Biol. 2008;84:348–56.PubMedPubMedCentralGoogle Scholar
  46. 46.
    Liu S, Lizée G, Lou Y, et al. Il-21 synergizes with IL-7 to augment expansion and anti-tumor function of cytotoxic T cells. Int Immunol. 2007;19:1213–21.PubMedGoogle Scholar
  47. 47.
    van Belle TL, Nierkens S, Arens R, et al. Interleukin-21 receptor-mediated signals control autoreactive T cell infiltration in pancreatic islets. Immunity. 2012;36:1060–72.PubMedGoogle Scholar
  48. 48.
    Shi F, Kong B-W, Song JJ, Lee JY, Dienglewicz RL, Erf GF. Understanding mechanisms of spontaneous autoimmune vitiligo development in the Smyth line chicken model by transcriptomic microarray analysis of evolving lesions. BMC Immunol. 2012;13:18.PubMedPubMedCentralGoogle Scholar
  49. 49.
    Austin LM, Boissy RE. Mammalian tyrosinase-related protein-1 is recognized by autoantibodies from vitiliginous Smyth chickens. An avian model for human vitiligo. Am J Pathol. 1995;146:1529–41.PubMedPubMedCentralGoogle Scholar
  50. 50.
    Searle EA, Austin LM, Boissy YL, et al. Smyth chicken melanocyte autoantibodies: cross-species recognition, in vivo binding, and plasma membrane reactivity of the antiserum. Pigment Cell Res. 1993;6:145–57.PubMedGoogle Scholar
  51. 51.
    Erf GF, Lockhart BR, Griesse RL, et al. Circulating melanocyte-specific autoantibodies and feather-infiltrating lymphocytes in young Smyth line chickens prior to visible onset of vitiligo. Pigment Cell Res. 2003;16:420–1.Google Scholar
  52. 52.
    Boissy RE, Smyth JR Jr, Fite KV. Progressive cytologic changes during the development of delayed feather amelanosis and associated choroidal defects in the DAM chicken line. Am J Pathol. 1983;111:197–212.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Boissy RE, Lamont SJ, Smyth JR Jr. Persistence of abnormal melanocytes in immunosuppressed chickens of the autoimmune “DAM” line. Cell Tissue Res. 1984;235:663–8.PubMedGoogle Scholar
  54. 54.
    Boissy RE, Moellmann G, Smyth JR Jr. Melanogenesis and autophagocytosis of melanin within feather melanocytes of delayed amelanotic (DAM) chickens. Pigment Cell. 1985;1:731–9.Google Scholar
  55. 55.
    Boissy RE, Moellmann G, Trainer AT, et al. Delayed-amelanotic (DAM or Smyth) chicken: melanocyte dysfunction in vivo and in vitro. J Invest Dermatol. 1986;86:149–56.PubMedGoogle Scholar
  56. 56.
    Erf GF, Wijesekera HD, Lockhart BR, et al. Antioxidant capacity and oxidative stress in the local environment of feather-melanocytes in vitiliginous Smyth line chickens. Pigment Cell Res. 2005;18:69.Google Scholar
  57. 57.
    Manga P, Sheyn D, Yang F, et al. A role for tyrosinase-related protein 1 in 4-tert-butylphenol-induced toxicity in melanocytes: implications for vitiligo. Am J Pathol. 2006;169:1652–62.PubMedPubMedCentralGoogle Scholar
  58. 58.
    Dong L, Dienglewicz RL, Erf GF. The response of melanocytes to 4-tertiary butylphenol is related to vitiligo susceptibility in the Smyth line chicken model for autoimmune vitiligo. Pigment Cell Melanoma Res. 2010;23:717.Google Scholar
  59. 59.
    Dong L, Dienglewicz RL, Erf GF. Divergent gene-expression profiles in 4-TBP-injected growing feathers of vitiligo-prone Smyth- and control chickens. Pigment Cell Melanoma Res. 2012;25:696–7.Google Scholar
  60. 60.
    Boyle ML III, Pardue SL, Smyth JR Jr. Effects of corticosterone on the incidence of amelanosis in Smyth delayed amelanotic line chickens. Poult Sci. 1987;66:363–7.PubMedGoogle Scholar
  61. 61.
    Fite KV, Pardue S, Bengston L, et al. Effects of cyclosporine in spontaneous, posterior uveitis. Curr Eye Res. 1986;5:787–96.PubMedGoogle Scholar
  62. 62.
    Lamont SJ, Smyth JR Jr. Effect of bursectomy on development of a spontaneous postnatal amelanosis. Clin Immunol Immunopathol. 1981;21:407–11.PubMedGoogle Scholar
  63. 63.
    Pardue SL, Fite KV, Bengston L, et al. Enhanced integumental and ocular amelanosis following termination of cyclosporine administration. J Invest Dermatol. 1987;88:758–61.PubMedGoogle Scholar
  64. 64.
    Boissy RE, Liu YY, Medrano EE, et al. Structural aberration of the rough endoplasmic reticulum and melanosome compartmentalization in long-term cultures of melanocytes from vitiligo patients. J Invest Dermatol. 1991;97:395–404.PubMedGoogle Scholar
  65. 65.
    Bowers RR, Gatlin JE. A simple method for the establishment of tissue culture melanocytes from regenerating fowl feathers. In Vitro Cell Dev Biol. 1985;21:39–44.PubMedGoogle Scholar
  66. 66.
    Le Poole IC, Boissy RE, Sarangarajan R, et al. PIG3V, an immortalized human vitiligo melanocyte cell line, expresses dilated endoplasmic reticulum. In Vitro Cell Dev Biol Anim. 2000;36:309–19.PubMedGoogle Scholar
  67. 67.
    Medrano EE, Nordlund JJ. Successful culture of adult human melanocytes obtained from normal and vitiligo donors. J Invest Dermatol. 1990;95:441–5.PubMedGoogle Scholar
  68. 68.
    Puri N, Phil M, Mojandar M, et al. In vitro growth characteristics of melanocytes obtained from adult normal and vitiligo subjects. J Invest Dermatol. 1987;88:434–8.PubMedGoogle Scholar
  69. 69.
    Erf GF, Bersi TK, Wang X, et al. Herpesvirus connection in the expression of autoimmune vitiligo in Smyth line chickens. Pigment Cell Res. 2001;14:40–6.PubMedGoogle Scholar
  70. 70.
    Calnek BW, Witter RL. Marek’s disease. In: Calnek BW, Barnes HJ, Beard CW, Reid WM, Yoder Jr HW, editors. Diseases of poultry. Ames, IA: Iowa State University Press; 1991.Google Scholar
  71. 71.
    Holland MS, Mackenzie CD, Bull RW, et al. Latent turkey herpesvirus infection in lymphoid, nervous, and feather tissues of chickens. Avian Dis. 1998;42:292–9.PubMedGoogle Scholar
  72. 72.
    Erf GF, Johnson JC, Parcells MS, et al. A role of turkey herpesvirus in autoimmune Smyth line vitiligo. In: Schat KA, editor. Current progress on avian immunology research. Jacksonville, FL: American Association of Avian Pathologists; 2001. p. 226–31.Google Scholar
  73. 73.
    Huett W, Byrne KA, Sorrick J, et al. Uveitis and blindness in Smyth line chickens with autoimmune vitiligo: expression of cytokine- and melanogenesis-related-genes in eyes before and during loss of choroidal melanocytes. Pigment Cell Melanoma Res. 2015;28:627.Google Scholar
  74. 74.
    Sorrick J, Dienglewicz RL, Erf GF. Uveitis and blindness in Smyth line chickens with autoimmune vitiligo: immunopathology associated with melanocyte loss in the eye. Pigment Cell Melanoma Res. 2013;26:769.Google Scholar
  75. 75.
    Overwijk WW, Tsung A, Irvine KR, et al. gp100/pmel 17 is a murine tumor rejection antigen: induction of “self”-reactive, tumoricidal T cells using high-affinity, altered peptide ligand. J Exp Med. 1998;188:277–86.PubMedPubMedCentralGoogle Scholar
  76. 76.
    International Chicken Polymorphism Map Consortium. A genetic variation map for chicken with 2.8 million single-nucleotide polymorphisms. Nature. 2004;432:717–22.PubMedCentralGoogle Scholar
  77. 77.
    Tang DC, DeVit M, Johnston SA. Genetic immunization is a simple method for eliciting an immune response. Nature. 1992;356:152–4.PubMedGoogle Scholar
  78. 78.
    Tüting T, Storkus WJ, Falo LD Jr. DNA immunization targeting the skin: molecular control of adaptive immunity. J Invest Dermatol. 1998;111:183–8.PubMedGoogle Scholar
  79. 79.
    Steitz J, Wenzel J, Gaffal E, et al. Initiation and regulation of CD8+ T cells recognizing melanocytic antigens in the epidermis: implications for the pathophysiology of vitiligo. Eur J Cell Biol. 2004;83:797–803.PubMedGoogle Scholar
  80. 80.
    Bowne WB, Srinivasan R, Wolchok JD, et al. Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med. 1999;190:1717–22.PubMedPubMedCentralGoogle Scholar
  81. 81.
    Engelhorn ME, Guevara-Patiño JA, Merghoub T, et al. Mechanisms of immunization against cancer using chimeric antigens. Mol Ther. 2008;16:773–81.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Overwijk WW, Theoret MR, Finkelstein SE, et al. Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells. J Exp Med. 2003;198:569–80.PubMedPubMedCentralGoogle Scholar
  83. 83.
    Weber LW, Bowne WB, Wolchok JD, et al. Tumor immunity and autoimmunity induced by immunization with homologous DNA. J Clin Invest. 1998;102:1258–64.PubMedPubMedCentralGoogle Scholar
  84. 84.
    Boissy RE, Manga P. On the etiology of contact/occupational vitiligo. Pigment Cell Res. 2004;17:208–14.PubMedGoogle Scholar
  85. 85.
    Kroll TM, Bommiasamy H, Boissy RE, et al. 4-Tertiary butyl phenol exposure sensitizes human melanocytes to dendritic cell-mediated killing, relevance to vitiligo. J Invest Dermatol. 2005;124:798–806.PubMedPubMedCentralGoogle Scholar
  86. 86.
    Namazi MR. Neurogenic dysregulation, oxidative stress, autoimmunity, and melanocytorrhagy in vitiligo: can they be interconnected? Pigment Cell Res. 2007;20:360–3.PubMedGoogle Scholar
  87. 87.
    Overwijk WW, Lee DS, Irvine KR, et al. Vaccination with a recombinant vaccinia virus encoding “self” antigen induces autoimmune vitiligo and tumor destruction in mice: requirement for CD4(+) T lymphocytes. Proc Natl Acad Sci U S A. 1999;96:2982–7.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Denman CJ, McCracken J, Hariharan V, et al. HSP70i accelerates depigmentation in a mouse model of autoimmune vitiligo. J Invest Dermatol. 2008;128:2041–8.PubMedPubMedCentralGoogle Scholar
  89. 89.
    Mosenson JA, Zloza A, Klarquist J, et al. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res. 2012;25:88–98.PubMedGoogle Scholar
  90. 90.
    Mosenson JA, Eby JM, Hernandez C, et al. A central role for inducible heat-shock protein 70 in autoimmune vitiligo. Exp Dermatol. 2013;22:566–9.PubMedPubMedCentralGoogle Scholar
  91. 91.
    Mosenson JA, Flood K, Klarquist J, et al. Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress. Pigment Cell Melanoma Res. 2014;27:209–20.PubMedPubMedCentralGoogle Scholar
  92. 92.
    You S, Cho Y-H, Byun J-S, et al. Melanocyte-specific CD8+ T cells are associated with epidermal depigmentation in a novel mouse model of vitiligo. Clin Exp Immunol. 2013;174:28–44.Google Scholar
  93. 93.
    Zhu Y, Wang S, Xu A. A mouse model of vitiligo induced by monobenzone. Exp Dermatol. 2013;22:482–501.Google Scholar
  94. 94.
    van den Boorn JG, Konijnenberg D, Tjin EP, et al. Effective melanoma immunotherapy in mice by the skin-depigmenting agent monobenzone and the adjuvants imiquimod and CpG. PLoS One. 2010;5:e10626.PubMedPubMedCentralGoogle Scholar
  95. 95.
    Westerhof W, Manini P, Napolitano A, et al. The haptenation theory of vitiligo and melanoma rejection: a close-up. Exp Dermatol. 2011;20:92–6.PubMedGoogle Scholar
  96. 96.
    Manga P, Orlow SJ. Engineering a new mouse model for vitiligo. J Invest Dermatol. 2012;132:1752–5.PubMedGoogle Scholar
  97. 97.
    Gregg RK, Nichols L, Chen Y, et al. Mechanisms of spatial and temporal development of autoimmune vitiligo in tyrosinase specific TCR transgenic mice. J Immunol. 2010;184:1909–17.PubMedPubMedCentralGoogle Scholar
  98. 98.
    Mehrotra S, Al-Khami AA, Klarquist J, et al. A coreceptor-independent transgenic human TCR mediates anti-tumor and anti-self immunity in mice. J Immunol. 2012;189:1627–38.PubMedPubMedCentralGoogle Scholar
  99. 99.
    Muranski P, Boni A, Antony PA, et al. Tumor-specific TH17-polarized cells eradicate large established melanoma. Blood. 2008;112:362–73.PubMedPubMedCentralGoogle Scholar
  100. 100.
    Kunisada T, Lu S-Z, Yoshida H, et al. Murine cutaneous mastocytosis and epidermal melanocytosis induced by keratinocyte expression of transgenic stem cell factor. J Exp Med. 1998;187:1565–73.PubMedPubMedCentralGoogle Scholar
  101. 101.
    Eby J, Kang H-K, Klarquist J, et al. Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation. Pigment Cell Melanoma Res. 2014;27:1075–785.PubMedPubMedCentralGoogle Scholar
  102. 102.
    Harris JE, Harris TH, Weninger W, et al. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8+ T cell accumulation in the skin. J Invest Dermatol. 2012;132:1869–76.PubMedPubMedCentralGoogle Scholar
  103. 103.
    Antony PA, Piccirillo CA, Akpinarli A, et al. CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cells. J Immunol. 2005;174:2591–601.PubMedPubMedCentralGoogle Scholar
  104. 104.
    Rashighi M, Agarwal P, Richmond JM, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014;6:223ra23.PubMedPubMedCentralGoogle Scholar
  105. 105.
    Agarwal P, Rashighi M, Essien KI, et al. Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo. J Invest Dermatol. 2015;135:1080–8.PubMedGoogle Scholar
  106. 106.
    Harris JE. IFN-γ in vitiligo, is it the fuel or the fire? Acta Derm Venereol. 2015;95:643–4.PubMedGoogle Scholar
  107. 107.
    Rashighi M, Harris JE. Interfering with the IFN-γ/CXCL10 pathway to develop new targeted treatments for vitiligo. Ann Transl Med. 2015;3:343–7.PubMedPubMedCentralGoogle Scholar
  108. 108.
    Lambe T, Leung JCH, Bouriez-Jones T, et al. CD4 cell-dependent autoimmunity against a melanocyte neoantigen induces spontaneous vitiligo and depends upon Fas-Fas ligand interactions. J Immunol. 2006;177:3055–62.PubMedGoogle Scholar
  109. 109.
    Chatterjee S, Eby J, Al-Khami AA, et al. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol. 2014;134:1285–94.PubMedGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Division of Agriculture, Center of Excellence for Poultry ScienceUniversity of ArkansasFayettevilleUSA
  2. 2.Robert H. Lurie Comprehensive Center, Department of Microbiology and ImmunologyNorth Western UniversityChicagoUSA

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