Type I interferon signaling limits viral vector priming of CD8+ T cells during initiation of vitiligo and melanoma immunotherapy

Rebecca L. Riding, Jillian M. Richmond, Keitaro Fukuda, John E. Harris

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


Vitiligo is an autoimmune skin disease in which epidermal melanocytes are targeted for destruction by CD8+ T cells specific for melanocyte/melanoma-shared antigens. IFNγ is the central cytokine driving disease, but the role of type I IFN in vitiligo remains unclear. We investigated the functional role of type I IFN during vitiligo progression using two different mouse models: one induced with a vaccinia virus (VV) vaccine and one induced with dendritic cells to prime autoimmune T cells. Induction of vitiligo by VV in IFNaR-deficient mice led to the development of severe vitiligo compared with wild-type (WT) mice and was characterized by a significantly enhanced effector CD8+ T-cell response. Severe vitiligo in this model was a result of VV persistence, because exacerbation of disease in IFNaR-deficient mice was not observed when antigen-pulsed dendritic cells were used to induce vitiligo instead of virus. Treatment of B16F10 melanoma-inoculated mice with VV vaccine therapy also induced a significantly enhanced anti-tumor response in IFNaR-deficient mice compared with WT. These results not only help define the pathways responsible for vitiligo progression but also suggest that blockade of type I IFNs following administration of a VV vaccine may provide increased immunogenicity and efficacy for melanoma immunotherapy.

Original languageEnglish
Pages (from-to)683-695
Number of pages13
JournalPigment Cell and Melanoma Research
Issue number4
Publication statusPublished - 2021 Jul
Externally publishedYes


  • CD8 T cells
  • autoimmunity
  • melanoma
  • type I interferon
  • vaccine immunotherapy
  • vaccinia virus
  • vitiligo

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology
  • Oncology
  • Dermatology


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