期刊
PIGMENT CELL & MELANOMA RESEARCH
卷 34, 期 4, 页码 683-695出版社
WILEY
DOI: 10.1111/pcmr.12935
关键词
autoimmunity; CD8 T cells; melanoma; type I interferon; vaccine immunotherapy; vaccinia virus; vitiligo
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [AR069114]
The study found that type I IFN plays an important role in the progression of vitiligo, and blocking type I IFNs may help improve the efficacy of melanoma immunotherapy, as shown by two different mouse models.
Vitiligo is an autoimmune skin disease in which epidermal melanocytes are targeted for destruction by CD8(+) T cells specific for melanocyte/melanoma-shared antigens. IFN gamma 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.
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