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Molecular mechanism of IgE-mediated FcεRI activation

ABSTRACT: The high-affinity Fc receptor for IgE, mainly present on mast cells and basophils, plays a crucial role in the development of allergic diseases. Monomeric IgE binding to receptor regulates mast cell survival, differentiation, and maturation. However, the underlying molecular mechanism remains unclear. Here we demonstrate that, prior to IgE binding, IgE receptor mostly exists as a homo-dimer on human mast cell membrane. The structure of human IgE receptor confirms the dimeric organization. Cholesterol-like molecules embedded within the transmembrane domain may stabilize the dimeric assembly. Upon IgE binding, the dimeric IgE receptor dissociates into two protomers, each binding to an IgE molecule. Importantly, this process elicits transcriptional activation of Egr1/3 and Ccl2 in rat basophils, which can be attenuated by inhibiting the IgE receptor dimer-to-monomer transition. Collectively, our study unveils the mechanism of antigen-independent, IgE-mediated receptor activation.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE278387 | GEO | 2024/11/30

REPOSITORIES: GEO

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