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FcγRIV is a mouse IgE receptor that resembles macrophage FcεRI in humans and promotes IgE-induced lung inflammation
David A. Mancardi, … , Marc Daëron, Pierre Bruhns
David A. Mancardi, … , Marc Daëron, Pierre Bruhns
Published October 23, 2008
Citation Information: J Clin Invest. 2008;118(11):3738-3750. https://doi.org/10.1172/JCI36452.
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Research Article Immunology Article has an altmetric score of 6

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

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Abstract

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.

Authors

David A. Mancardi, Bruno Iannascoli, Sylviane Hoos, Patrick England, Marc Daëron, Pierre Bruhns

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Figure 7

mFcγRIV engagement by IgE ICs in vivo promotes lung infiltration.

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mFcγRIV engagement by IgE ICs in vivo promotes lung infiltration.
(A) mF...
(A) mFcεRI–/–mCD23–/– mice were instilled i.n. with IgEa anti-OVA (2C6a), Ag (OVA), preformed IgEa ICs (2C6a-OVA) (n = 7), or LPS (n = 2) (first panel), or with cell-free supernatants corresponding to indicated numbers of unstimulated (Unsti.) or activated WT BMMCs (cell equivalent [eq.] × 10–6) (n = 2) (second panel) on day 0. Bold is used to indicate the dose used in B and C. mFcεRI–/–mCD23–/– mice were instilled i.n. with the same cell-free supernatants (sup.) corresponding to 2.5 × 106 activated BMMCs on day 0 (a dose that does not induce a significant infiltration [1%] compared with that induced by supernatant from unstimulated BMMCs) and with preformed IgEa ICs on day 1 as indicated. Bar graphs represent the percentage of Mac1+ Gr1+ in BAL from these mice 24 hours after i.n. instillation (3 left panels) or the percentage of polynuclear cells in cytospins of BAL (right panel) on day 3. (B and C) Quintuple-KO (n = 5) or FcRγ–/– (n = 3) mice were instilled i.n. with the same cell-free supernatants as in A, corresponding to 2.5 × 106 activated BMMCs on day 0, and with preformed IgEa ICs (2C6a-OVA) on day 1. A representative density plot of BAL cells from these mice on day 2 for each experimental condition is shown. Bar graphs represent the percentage of Mac1+ Gr1+ in BAL or the percentage of polynuclear cells in cytospins of BAL. Error bars represent mean ± SD (A–C) and significant differences between sample means are indicated (***P < 0.001; **P ≤ 0.01; *P < 0.05; n.s., P > 0.05; Student’s t test).

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ISSN: 0021-9738 (print), 1558-8238 (online)

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