Vaccinia virus, a cowpox virus used to vaccinate against smallpox, can be lethal for people with the skin disease atopic dermatitis (AD). On page 1219, Kawakami and colleagues show that the cytokine IL-17A amplifies vaccinia virus infection by muffling natural killer (NK) cells.
When vaccinated, AD patients often develop eczema vaccinatum, a severe reaction characterized by erosive rashes. Although these patients are known to have increased levels of IL-17 in the skin and dysfunctional NK cells, it was unclear whether these observations were connected. Here, Kawakami et al. describe a new mouse model that mimics aspects of the human condition, allowing them to establish a link between IL-17 and NK cell defects. Excess IL-17A—but not IL-17F—suppressed NK cell activity, which increased virus titers and skin lesion size in mice with eczema.
The mice were protected when the authors neutralized IL-17A or injected activated NK cells. These treatments revived NK cell cytolytic activity and increased interferon-γ production. IL-17A may directly inhibit NK cells, as adding IL-17 to NK cell cultures in vitro inhibited the expression of interferon-γ, perforin, and granzyme B. IL-17 might also act indirectly through the type I interferons known to activate NK cells. What causes the initial boost in IL-17–secreting cells during the acute response to vaccination in mice with eczema remains unknown.
