High-affinity immunoglobulin E receptor (FcεRI) and Immunoglobulin E (IgE) signaling axis (FcεRI-IgE axis)

The Allergen-specific IgE–FcεRI–mast cell/basophil axis is the primary pathway responsible for Type I hypersensitivity and allergic inflammation (Galli et al., Nature, 2008). This axis is initiated when allergen-specific Immunoglobulin E (IgE) antibodies bind to the high-affinity IgE receptor (FcεRI) on the surface of mast cells and basophils (UniProt: P12319). Upon re-exposure to the allergen, the IgE-FcεRI complexes are cross-linked, triggering an intracellular signaling cascade involving kinases like Spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) (Siraganian et al., Immunol Rev, 2010). This activation leads to the immediate release of preformed mediators like histamine and the synthesis of lipid mediators and cytokines, which drive the clinical symptoms of asthma, allergic rhinitis, and anaphylaxis (NIH: NIAID Allergic Reaction). Therapeutic intervention often focuses on neutralizing free IgE using monoclonal antibodies like omalizumab, which prevents IgE from binding to its receptor and subsequently leads to the downregulation of FcεRI on effector cells (FDA: Xolair Prescribing Information). Newer approaches target the intracellular signaling components of the axis, such as BTK inhibitors, to block the degranulation process directly (ClinicalTrials.gov: NCT04668300).

Other names

IgE-FcεRI pathwayType I hypersensitivity pathwayMast cell activation pathwayIgE-mediated allergic cascadeAllergen-specific IgE-FcεRI-mast cell/basophil axis

Inhibition of IgE binding to the high-affinity receptor (FcεRI) or inhibition of downstream signaling kinases (e.g., BTK, SYK) to prevent mast cell and basophil activation.