IgE-Mediated Activation of NK Cells Through FcγRIII

Abstract

NK cells express FcγRIII (CD16), which is responsible for IgG-dependent cell cytotoxicity and for production of several cytokines and chemokines. Whereas FcγRIII on NK cells is composed of both FcγRIIIα and FcRγ chains, that on mast cells is distinct from NK cells and made of FcγRIIIα, FcRβ, and FcRγ. Mast cells show degranulation and release several mediators, which cause anaphylactic responses upon cross-linking of FcγRIII as well as FcεRI with aggregated IgE. In this paper, we examined whether IgE activates NK cells through FcγRIII 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 FcγRIII-dependent manner. These effects of IgE through FcγRIII were not observed in NK cells from FcRγ-deficient mice lacking FcγRIII expression. Collectively, these results demonstrate that NK cells can be activated with IgE through FcγRIII 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.

Interaction of KIR Genes and G1M Immunoglobulin Allotypes Confer Susceptibility to Type 2 Diabetes in Puerto Rican Americans

“…Our observations led us to conclude that interactions between GM allotypes and KIR genes may contribute to the generation of an immune-mediated type 2 diabetes. For example, Ig allotypes and KIR genes could influence humoral and NK cell immunity against antigens of the islets of Langerhans, which is consistent with specific KIR-MHC interactions in autoimmune diseases [45], and the possible role of antibodies in the recruitment of NK cells together with antibodydependent cellular cytotoxicity mediated by NK cells through Fc␥R [46]. In summary, we described an epistatic interaction between KIR genes and the G1M allotypes associated with T2D in Puerto Rican Americans.…”

A Novel Pathway of Chronic Allograft Rejection Mediated by NK Cells and Alloantibody

“…This mechanism is relevant to the “hybrid resistance” of F1 recipients to parental bone marrow transplants and the CAV that develops in parent to F1 heart allografts. In contrast, ADCC is triggered by interaction of Fcγ RIII on NK cells with immunoglobulin bound to antigen on target cells, leading to NK activation (25,26). NK cells, by their Fc receptors, are necessary for hyperacute xenograft rejection mediated by noncomplement fixing anti-Gal antibodies (12).…”

Natural killer cells

“…NK cells are indicated to generate IFN-c, TNF-a, GM-CSF and MIP-1 a upon stimulation with IgE, and also demonstrate cytotoxicity against IgE coated target cells in a Fc cRIII dependent manner. 76 NK cells interact with various other immune cells in our body both in normal conditions as well as during pathological conditions. In normal and asthmatic lungs, lung resident dendritic cells and macrophages are known to form synapses with NK cells leading to generation of NK derived cytokines and effector molecules involved in local immunity, and at the same time can regulate allergic disease severity.…”