Siglec-E

Siglec-E is the principal inhibitory Siglec of mice, functionally orthologous to the human Siglec-9, and is a key model for studying CD33-related Siglec biology in vivo. Siglec-E is a type I transmembrane protein expressed on neutrophils, monocytes, macrophages, dendritic cells and eosinophils; its V-set domain binds α2,3-linked sialylated glycans, including sialylated lactosamine structures, and its cytoplasmic tail contains ITIM and ITIM-like motifs that recruit SHP-1/SHP-2 to dampen tyrosine kinase signaling. Siglec-E restrains neutrophil recruitment, oxidative burst and NETosis during sterile and infectious inflammation, suppresses TLR-driven dendritic cell activation and limits inflammasome activity. Siglec-E-deficient mice exhibit enhanced inflammatory responses, accelerated arthritis, neuroinflammation and metabolic inflammation, and increased antitumor immunity in sialylated tumor models. The receptor also mediates group B Streptococcus immune evasion via sialylated capsule engagement. Siglec-E research established the glyco-immune checkpoint concept of tumor hypersialylation suppressing myeloid cells, guiding translational work on human Siglec-7/9 blockade.