IgE-mediated activation of NK cells through FcγRIII

NK cells express FcgammaRIII (CD16), which is responsible for IgG-dependent cell cytotoxicity and for production of several cytokines and chemokines. Whereas FcgammaRIII on NK cells is composed of both FcgammaRIIIalpha and FcRgamma chains, that on mast cells is distinct from NK cells and made of FcgammaRIIIalpha, FcRbeta, and FcRgamma. Mast cells show degranulation and release several mediators, which cause anaphylactic responses upon cross-linking of FcgammaRIII as well as FcepsilonRI with aggregated IgE. In this paper, we examined whether IgE activates NK cells through FcgammaRIII on their cell surface. We found that NK cells produce several cytokines and chemokines related to an allergic reaction upon IgE stimulation. Furthermore, NK cells exhibited cytotoxicity against IgE-coated target cells in an FcgammaRIII-dependent manner. These effects of IgE through FcgammaRIII were not observed in NK cells from FcRgamma-deficient mice lacking FcgammaRIII expression. Collectively, these results demonstrate that NK cells can be activated with IgE through FcgammaRIII and exhibit both cytokine/chemokine production and Ab-dependent cell cytotoxicity. These data imply that not only mast cells but also NK cells may contribute to IgE-mediated allergic responses.