Original Article
Autoimmunity/Autoinflammation
NKG2D Defines a Subset of Skin Effector Memory CD8 T Cells with Proinflammatory Functions in Vitiligo

https://doi.org/10.1016/j.jid.2019.11.013Get rights and content
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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.

Abbreviations

DC
dendritic cell
JAK
Janus kinase
mAb
monoclonal antibody
Mo-DC
monocyte-derived dendritic cell
NK
natural killer
TEM cell
effector memory T cell
TNF-α
tumor necrosis factor-α

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See related commentary on pg 1131