FcγRIV is a recently identified mouse activating receptor for IgG2a and IgG2b that is expressed on monocytes, macrophages, and neutrophils; herein it is referred to as mFcγRIV. Although little is known about mFcγRIV, it has been proposed to be the mouse homolog of human FcγRIIIA (hFcγRIIIA) because of high sequence homology. Our work, however, has revealed what we believe to be new properties of mFcγRIV that endow this receptor with a previously unsuspected biological significance; we have shown that it is a low-affinity IgE receptor for all IgE allotypes. Although mFcγRIV functioned as a high-affinity IgG receptor, mFcγRIV-bound monomeric IgGs were readily displaced by IgE immune complexes. Engagement of mFcγRIV by IgE immune complexes induced bronchoalveolar and peritoneal macrophages to secrete cytokines, suggesting that mFcγRIV may be an equivalent of human FceRI(αγ), which is expressed by macrophages and neutrophils and especially in atopic individuals, rather than an equivalent of hFcγRIIIA, which has no affinity for IgE. Using mice lacking 3 FcγRs and 2 FceRs and expressing mFcγRIV only, we further demonstrated that mFcγRIV promotes IgE-induced lung inflammation. These data lead us to propose a mouse model of IgE-induced lung inflammation in which cooperation exists between mast cells and mFcγRIV-expressing lung cells. We therefore suggest that a similar cooperation may occur between mast cells and hFceRI-expressing lung cells in human allergic asthma.
David A. Mancardi, Bruno Iannascoli, Sylviane Hoos, Patrick England, Marc Daëron, Pierre Bruhns
Both hFcεRI and mFcγRIV engagement by IgE ICs induces TNF-α secretion by peritoneal macrophages.