NKG2D Defines a Subset of Skin Effector Memory CD8 T Cells with Proinflammatory Functions in Vitiligo

This is the authors' abstract. We don't add key points for this paper.

Vitiligo is an autoimmune disease that results from the loss of melanocytes, associated with skin infiltration of CD8 + effector memory T cells with a Tc1 skewed immune response. NKG2D is an activating receptor found on immune cells, in particular natural killer and activated CD8 + T cells, that are able to produce a high amount of IFN-γ. Here we found that NKG2D expression was increased in vitiligo skin CD8 + effector memory T cells and was promoted by IL-15. Phenotypic and functional analyses showed that NKG2D + CD8 + skin effector memory T cells displayed an activated phenotype and produced elevated levels of both IFN-γ and tumor necrosis factor-α. Additional experiments revealed that vitiligo skin dendritic cells expressed the NKG2D ligands MICA-MICB, and in vitro experiments showed that these ligands could be induced on dendritic cells by IFN-α. Cultures of IFN-α–stimulated dendritic cells with skin NKG2D + CD8 + T cells potentiated the production of type 1 cytokines, which was next inhibited by blocking the NKG2D/MICA-MICB interaction. These data show that NKG2D is a potential marker of pathogenic skin CD8 + effector memory T cells during vitiligo. Therefore, targeting NKG2D could be an attractive strategy in vitiligo, a disease for which there is a strong need of innovative treatments.