The IgE-mediated and Th2-dependent late-phase reaction remains a mechanistically enigmatic and daunting element of human allergic inflammation. In this study, we uncover the FcεRI on dendritic cells (DCs) as a key in vivo component of this form of allergy. Because rodent, unlike human, DCs lack FcεRI, this mechanism could be revealed only by using a new transgenic mouse model with human-like Fc...

Elevated IgE levels and increased IgE sensitization to allergens are central features of allergic asthma. IgE binds to the high affinity IgE receptor FcεRI on mast cells , basophils , and dendritic cells , and mediates the activation of these cells upon antigeninduced crosslinking of IgE-bound FcεRI. FcεRI activation proceeds through a network of signaling molecules and adaptor proteins and is ...

Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcεRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcεRI and omalizumab-binding sites in the Cε3 domain, but crystallographic studies show FcεRI and CD23-binding sites tha...

Elevated IgE levels and increased IgE sensitization to allergens are central features of allergic asthma. IgE binds to the high affinity IgE receptor FcεRI on mast cells , basophils , and dendritic cells , and mediates the activation of these cells upon antigeninduced crosslinking of IgE-bound FcεRI. FcεRI activation proceeds through a network of signaling molecules and adaptor proteins and is ...

Cross-linking of immunoglobulin E-bound FcεRI triggers multiple cellular responses, including degranulation and cytokine production. Signaling is dependent on recruitment of Syk via docking of its dual SH2 domains to phosphorylated tyrosines within the FcεRI immunoreceptor tyrosine-based activation motifs. Using single-molecule imaging in live cells, we directly visualized and quantified the bi...

FcεRI, which is composed of α, β, and γ subunits, plays an important role in IgE-mediated allergic responses. TGF-β1 has been reported to suppress FcεRI and stem cell factor receptor c-Kit expression on mast cell surfaces and to suppress mast cell activation induced by cross-linking of FcεRI. However, the molecular mechanism by which these expressions and activation are suppressed by TGF-β1 rem...

The role of the IgE-FcεRI complex in malaria severity in Plasmodium falciparum-hosting patients is unknown. We demonstrate that mice genetically deficient for the high-affinity receptor for IgE (FcεRIα-KO) or for IgE (IgE-KO) are less susceptible to experimental cerebral malaria (ECM) after infection with Plasmodium berghei (PbANKA). Mast cells and basophils, which are the classical IgE-express...

Ethanol has multiple effects on biochemical events in a variety of cell types, including the high-affinity immunoglobulin E receptor (FcεRI) signaling in antigen-activated mast cells. However, the underlying molecular mechanism remains unknown. To get better understanding of the effect of ethanol on FcεRI-mediated signaling we examined the effect of short-term treatment with non-toxic concentra...

IgE, the antibody that mediates allergic responses, acts as part of a self-regulating protein network. Its unique effector functions are controlled through interactions of its Fc region with two cellular receptors, FcεRI on mast cells and basophils and CD23 on B cells. IgE cross-linked by allergen triggers mast cell activation via FcεRI, whereas IgE-CD23 interactions control IgE expression leve...

Immunoglobulin E (IgE) and its high-affinity receptor (FcεRI) are well-known participants in the allergic response. The interaction of allergens with FcεRI-bound IgE antibodies is an essential step in mast cell/basophil activation and the subsequent release of allergic mediators. It is known that the affinity of the interaction between an IgE antibody and an allergen may differ, raising the que...