Sialic acid-binding immunoglobulin-like lectin F (Siglec-F)

Sialic acid-binding immunoglobulin-like lectin F (Siglec-F) is a single-pass type I transmembrane protein that belongs to the immunoglobulin superfamily and is part of the Siglec family of sialic acid–binding receptors. It is predominantly expressed on murine eosinophils and to a lesser extent on alveolar macrophages, featuring multiple immunoglobulin-like extracellular domains with an N-terminal carbohydrate-binding domain and an intracellular tail containing an immunoreceptor tyrosine-based inhibition motif (ITIM). Siglec-F selectively binds α2,3-linked sialic acid–containing glycans, with 6′-sulfated sialyl Lewis X as a preferred ligand, leading to receptor-mediated suppression and induction of apoptosis in eosinophils. The engagement of Siglec-F by endogenous glycoprotein ligands or experimental agonists is a proposed mechanism for regulating eosinophil survival and accumulation in diseases such as asthma and other allergic inflammatory conditions. No direct human therapeutic agents target Siglec-F, but its human functional paralogue Siglec-8 is under investigation for related immune-modulating therapies.

Other names

Siglec-FSialic acid-binding Ig-like lectin FSiglecf (gene name)

Induction of apoptosis or depletion of eosinophils (via ligand binding by glycomimetic agonists or monoclonal antibodies). Immune response inhibition (downregulation of activating signaling when ITIMs are phosphorylated).