sialoadhesins

Sialoadhesins are a subfamily of immunoglobulin superfamily members that function as sialic acid–binding lectins on leukocyte surfaces. The family includes proteins such as CD33 (Siglec-3), CD169 (Siglec-1), CD172a (Siglec-5), and CD169e (Siglec-7). Each sialoadhesin contains an extracellular domain composed of an N‑terminal V-set immunoglobulin domain followed by multiple C2‑type Ig-like domains, a transmembrane segment, and a short cytoplasmic tail that may contain immunoreceptor‑tyrosine–based inhibitory motifs (ITIMs). The N‑terminal domain confers specificity for α2,3‑ or α2,6‑linked sialic acids on glycoproteins and glycolipids.

Sialoadhesins are expressed predominantly on myeloid cells, including macrophages, microglia, and dendritic cells, and play roles in cell adhesion, antigen presentation, and modulation of inflammatory responses. By binding sialylated ligands on target cells or pathogens, they can mediate leukocyte rolling, firm adhesion, and phagocytosis. Signal transduction through intracellular ITIMs recruits phosphatases such as SHP-1 and SHP-2, dampening activation signals and maintaining immune homeostasis. Alterations in sialoadhesin expression are associated with autoimmune diseases, infections, and cancer, making them potential therapeutic targets.

The nomenclature of sialoadhesins follows the Siglec (sialic acid–binding immunoglobulin-like lectin) classification. Structural studies have revealed a conserved calcium‑binding site within the V-set domain that stabilizes contact with sialic acid, and mutations in this motif abolish lectin activity. In vitro and in vivo analyses demonstrate that sialoadhesins can influence leukocyte migration, cytokine production, and vaccine efficacy. Research continues to elucidate their precise roles in disease contexts and their viability as drug targets.