title: Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation.
abstract: To generate a mouse model of spontaneous epidermal depigmentation, parental h3TA2 mice, expressing both a human-derived, tyrosinase-reactive T-cell receptor on T cells and the matching HLA-A2 transgene, were crossed to keratin 14-promoter driven, stem cell factor transgenic (K14-SCF) mice with intra-epidermal melanocytes. In resulting Vitesse mice, spontaneous skin depigmentation precedes symmetrical and sharply demarcated patches of graying hair. Whereas the SCF transgene alone dictates a greater retinoic acid receptor-related orphan receptor gamma (RORγt)(+) T-cell compartment, these cells displayed markedly increased IL-17 expression within Vitesse mice. Similar to patient skin, regulatory T cells were less abundant compared with K14-SCF mice, with the exception of gradually appearing patches of repigmenting skin. The subtle repigmentation observed likely reflects resilient melanocytes that coexist with skin-infiltrating, melanocyte-reactive T cells. Similar repigmenting lesions were found in a different TCR transgenic model of vitiligo developed on an SCF transgenic background, supporting a role for SCF in repigmentation.
authors.affiliation: Oncology Research Institute, Loyola University Chicago, Chicago, IL, USA.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Eby
authors.forename: Hee-Kap
authors.initials: HK
authors.lastname: Kang
authors.forename: Jared
authors.initials: J
authors.lastname: Klarquist
authors.forename: Shilpak
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Mosenson
authors.forename: Michael I
authors.initials: MI
authors.lastname: Nishimura
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Garrett-Mayer
authors.forename: B Jack
authors.initials: BJ
authors.lastname: Longley
authors.forename: Victor H
authors.initials: VH
authors.lastname: Engelhard
authors.forename: Shikhar
authors.initials: S
authors.lastname: Mehrotra
authors.forename: I Caroline
authors.initials: IC
authors.lastname: Le Poole
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004817:Epidermis / Q000473:pathology*; D000939:Epitopes; D006801:Humans; D017496:Hypopigmentation / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D007109:Immunity; D020381:Interleukin-17 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D014442:Monophenol Monooxygenase / Q000378:metabolism; D010858:Pigmentation; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D019089:Stem Cell Factor / Q000235:genetics; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019076:Transgenes; D014820:Vitiligo / Q000150:complications* / Q000276:immunology* / Q000473:pathology
chemical_list: D000939:Epitopes; D020381:Interleukin-17; D011948:Receptors, Antigen, T-Cell; D019089:Stem Cell Factor; D014442:Monophenol Monooxygenase
keywords: IL-17; T-cell receptor; mouse model; pigmentation; stem cell factor; vitiligo