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Adhesion G protein-coupled receptor E1 (ADGRE1), also known as EMR1, is a member of the adhesion G protein-coupled receptor family characterized by a large extracellular domain containing multiple epidermal growth factor (EGF)-like repeats (UniProtKB Q14246). In humans, ADGRE1 is uniquely and highly expressed on the surface of eosinophils, serving as a highly specific phenotypic marker for these cells, whereas its mouse ortholog, F4/80, is a well-established marker for mature macrophages (Hamann et al., 2007, PNAS). The receptor is involved in immune cell adhesion and signal transduction, although its specific endogenous ligands remain largely uncharacterized (Langenhan et al., 2013, Nat Rev Mol Cell Biol). Due to its restricted expression on human eosinophils, ADGRE1 is considered a promising therapeutic target for eosinophil-driven inflammatory diseases, such as asthma, hypereosinophilic syndrome, and eosinophilic esophagitis (Legrand et al., 2010, J Allergy Clin Immunol). Therapeutic strategies under investigation primarily focus on the development of monoclonal antibodies designed to deplete eosinophils via antibody-dependent cellular cytotoxicity or to modulate their activation (Waddell et al., 2018, Sci Rep). Understanding the role of ADGRE1 in the tumor microenvironment is also an area of active research, as eosinophils can influence cancer progression and response to immunotherapy (Grisaru-Tal et al., 2020, Front Immunol). Its structural complexity, including a GPCR autoproteolysis-inducing (GAIN) domain, suggests it may function as a mechanosensor or environmental sensor within the immune system. Overall, ADGRE1 represents a specific molecular handle for modulating eosinophil activity in various pathological states.
Antibody-dependent cellular cytotoxicity (ADCC) and receptor-mediated signaling modulation
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