FcγRIV is a mouse IgE receptor that resembles macrophage FcεRI in humans and promotes IgE-induced lung inflammation

Fc gamma RIV is a recently identified mouse activating receptor for IgG2a and lgG2b that is expressed on monocytes, macrophages, and neutrophils; herein it is referred to as mFc gamma RIV. Although little is known about mFc gamma RIV, it has been proposed to be the mouse homolog of human Fc gamma RIIIA (hFc gamma RIIIA) because of high sequence homology. Our work, however, has revealed what we believe to be new properties of mFc gamma RIV 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 mFc gamma RIV functioned as a high-affinity IgG receptor, mFc gamma RIV-bound monomeric IgGs were readily displaced by IgE immune complexes. Engagement of mFc gamma RIV by IgE immune complexes induced bronchoalveolar and peritoneal macrophages to secrete cytokines, suggesting that mFc gamma RIV may be an equivalent of human Fc epsilon RI(cry), which is expressed by macrophages and neutrophils and especially in atopic individuals, rather than an equivalent of hFc gamma RIIIA, which has no affinity for IgE. Using mice lacking 3 Fc gamma Rs and 2 Fc epsilon Rs and expressing mFc gamma RIV only, we further demonstrated that mFc gamma RIV 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 mFc gamma RIV-expressing lung cells. We therefore suggest that a similar cooperation may occur between mast cells and hFc epsilon RI-expressing lung cells in human allergic asthma.