Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation

Jonathan M. Eby, Hee Kap Kang, Jared Klarquist, Shilpak Chatterjee, Jeffrey A. Mosenson, Michael I. Nishimura, Elizabeth Garrett-Mayer, B. Jack Longley, Victor H. Engelhard, Shikhar Mehrotra, I. Caroline Le Poole*

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1075-1085
Number of pages11
JournalPigment Cell and Melanoma Research
Volume27
Issue number6
DOIs
StatePublished - Nov 1 2014

Keywords

  • IL-17
  • Mouse model
  • Pigmentation
  • Stem cell factor
  • T-cell receptor
  • Vitiligo

ASJC Scopus subject areas

  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Dermatology

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  • Cite this

    Eby, J. M., Kang, H. K., Klarquist, J., Chatterjee, S., Mosenson, J. A., Nishimura, M. I., Garrett-Mayer, E., Longley, B. J., Engelhard, V. H., Mehrotra, S., & Le Poole, I. C. (2014). Immune responses in a mouse model of vitiligo with spontaneous epidermal de- and repigmentation. Pigment Cell and Melanoma Research, 27(6), 1075-1085. https://doi.org/10.1111/pcmr.12284