Sialic acid-binding immunoglobulin-like lectin 11 (SIGLEC11)

Sialic acid-binding immunoglobulin-like lectin 11 (SIGLEC11) is a member of the IG superfamily localized on the surface of innate immune cells, including tissue macrophages and, uniquely in humans, microglia. SIGLEC11 recognizes alpha-2,8-linked sialic acids on glycoproteins through its extracellular Ig-like domains, serving to modulate immune cell reactivity. Upon ligand binding, it recruits SHP-family tyrosine phosphatases via its intracellular motifs, leading to immunosuppressive and anti-inflammatory signaling. In microglia, SIGLEC11 exists as a splice variant missing the last Ig-like domain, which alters its ligand-binding, secretion, and exosomal export properties. SIGLEC11's unique human brain expression and regulation by gene conversion events may be relevant to neuroinflammatory and neurodegenerative diseases, but therapeutic exploitation is currently limited by immunological complexity and species specificity[4][1][3][2].

Other names

Sialic acid-binding Ig-like lectin 11Siglec-11Sialic acid-binding lectin 11UNQ9222/PRO28718SIGLEC11

For drugs targeting this molecule (none currently approved), the expected mechanism would be modulation of immune cell signaling through ligand binding, recruitment of SHP-1/2 phosphatases, and attenuation of activation pathways in microglia/macrophages[4][1]. - Siglec-11 acts as an inhibitory receptor; ligand engagement leads to tyrosine phosphorylation and downstream recruitment of phosphatases that block signal transduction[4].