IL-4 selectively enhances FcγRIII expression and signaling on mouse mast cells

Abstract

Fc receptors for IgG (FcγR) are widely expressed in the hematopoietic system and mediate a variety of inflammatory responses. There are two functional classes of FcγR, activation and inhibitory receptors. Since IgG immune complexes (IgG IC) bind each class with similar affinity, co-expression of these receptors leads to their co-ligation. Thus, expression levels of this antagonistic pair play a critical role in determining the cellular response. Murine mast cells co-express the activation receptor FcγRIII and the inhibitory receptor FcγRIIb and can be activated by IgG IC. Mast cell activation contributes to allergic and other inflammatory diseases—particularly those in which IgG IC may play important roles. Using mouse bone marrow-derived mast cells, we report that IL-4 selectively increases FcγRIII expression without altering FcγRIIb. This enhanced expression could be induced by Stat6 activation alone, and appeared to be mediated in part by increased FcγRIIIα protein synthesis without significant changes in transcription. The increase in FcγRIII expression was functionally significant, as it was matched by enhanced FcγR-mediated degranulation and cytokine production. Selective regulation of mast cell FcγR by interleukin-4 could alter inflammatory IgG responses and subsequently disease severity and progression.