IL-10 Inhibits FcεRI Expression in Mouse Mast Cells

Abstract

FcεRI expression and function is a central aspect of allergic disease. Using bone marrow-derived mouse mast cell populations, we have previously shown that the Th2 cytokine IL-4 inhibits FcεRI expression and function. In the current study we show that the Th2 cytokine IL-10 has similar regulatory properties, and that it augments the inhibitory effects of IL-4. FcεRI down-regulation was functionally significant, as it diminished inflammatory cytokine production and IgE-mediated FcεRI up-regulation. IL-10 and IL-4 reduced FcεRI β protein expression without altering the α or γ subunits. The ability of IL-4 and IL-10 to alter FcεRI expression by targeting the β-chain, a critical receptor subunit known to modulate receptor expression and signaling, suggests the presence of a Th2 cytokine-mediated homeostatic network that could serve to both initiate and limit mast cell effector function.

The high-affinity IgE receptor (FcεRI): a critical regulator of airway smooth muscle cells?

“…Cytokines, particularly IL-4, have been shown to play a positive role in the transcription of Fc⑀RI ␣-chain in human mast cells (106), human eosinophils from atopic dermatitis subjects (104), and human dendritic cells (30). In mice, however, IL-4 and also IL-10 decrease Fc⑀RI expression specifically affecting FcR ␤-, but not FcR ␣-or FcR ␥-, subunits (32,93).…”

Cutting Edge: CD4 T Cell-Mast Cell Interactions Alter IgE Receptor Expression and Signaling

“…Because we have found that the cytokines IL-10 and TGF␤1, which are produced by Treg, can suppress mast cell function (15)(16)(17)(18)(19)(20)(21)(22), we investigated how Tregmast cell interactions affect the mast cell response. Mast cell activation by IgE logically precedes inflammation in atopic disease, suggesting that mast cells could elicit Treg migration.…”

“…Given that suppression by preactivated Treg is both Ag and MHC nonspecific, these potent inhibitory cytokines may be critical depending upon the disease model used. We have found that IL-10 and TGF␤1 inhibit mast cell development, function, and survival (15)(16)(17)(18)(19)(20)(21)(22). We have now investigated the role of Treg in controlling the mast cell response.…”

Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

“…Immunoprecipitation of Fc RI ␣ from lung cDCs and MC/9 mast cells was performed as previously described ( 44,45 ). In brief, 3 ϫ 10 6 cells were solubilized in 100 mM Tris containing 0.5% Nonidet P-40, 10% glycerol, 5 M NaCl, 100 mM MgCl 2 , and enhanced inhibitor supplement consisting of a 20 ϫ concentrate of complete edium (80 mM benzamidine HCL, 50 mM -caproic acid, 16 mM iodoacetamide, 10 g/ml leupeptin, 10 g/ml pepstatin, and 100 g/ml soybean trypsin inhibitor).…”