Sialic acid-binding Ig-like lectin F receptor (Siglec-F) (Siglec-F)

Sialic acid-binding Ig-like lectin F receptor (Siglec-F) is a mouse-specific, single-pass type I transmembrane protein belonging to the immunoglobulin superfamily and classified as a CD33-related Siglec (CD33rSiglec)[3]. It consists of four extracellular immunoglobulin-like domains, a transmembrane domain, and a cytoplasmic tail containing two immunoreceptor tyrosine-based inhibitory motifs (ITIMs)[3]. Siglec-F is primarily expressed on mature eosinophils and alveolar macrophages[3][5]. It preferentially binds α2,3-linked sialic acid, with a high affinity for 6′sulfo-sialyl-Lewis X[3][5]. Siglec-F functions as an inhibitory receptor: engagement by its natural ligands or by antibodies induces apoptosis in eosinophils, suggesting a role in the negative regulation of eosinophilic inflammation[3][5]. Siglec-F is not a direct ortholog of any human protein; however, its expression pattern and function closely resemble those of human Siglec-8, making it a valuable model for studying eosinophil biology and allergic inflammation[5]. Mouse Siglec-F has been implicated in in vivo negative feedback regulation of eosinophilic responses in murine models of asthma and allergic inflammation, but clinical relevance in humans is limited by the absence of a true ortholog[5]. The receptor’s targeting in mice is primarily experimental, with no approved drugs for clinical use. Safety concerns relate to the risk of unintended immunosuppression, and biomarker utility is currently confined to research settings.

Other names

CD170Siglec5Siglecf

Antibody-mediated receptor engagement leading to apoptosis; Immunosuppressive signaling through ITIM motifs