IL-4 Inhibits Mouse Mast Cell FcεRI Expression Through a STAT6-Dependent Mechanism

Abstract

Abstract Mast cell activation by IgE-mediated stimuli is a central event in atopic disease. The regulation of the mast cell high affinity receptor, FcεRI, is poorly understood. We show that IL-4 can inhibit FcεRI expression on mouse bone marrow-derived mast cells and fetal liver-derived mast cell progenitors. This effect could be observed at 2.5 ng/ml IL-4 and was dose dependent. IL-4-mediated inhibition of cultured BMMC required 4 days of stimulation and was sustained at maximum levels for at least 21 days. The inhibition of FcεRI expression resulted in decreased sensitivity to IgE-mediated stimulation, as measured by serotonin release, and the induction of mRNA for IL-4, IL-5, IL-6, and IL-13. Additionally, IL-4 could abrogate the IgE-mediated increase in FcεRI expression. Lastly, IL-4-mediated inhibition was dependent upon expression of the STAT6 transcription factor, as STAT6-deficient bone marrow-derived mast cells did not decrease FcεRI levels in response to IL-4. These data argue for a homeostatic role of IL-4 in the regulation of FcεRI expression, a role that could be critical to understanding atopic disease.