Sialic acid-binding immunoglobulin-like lectin (Siglec)

Sialic acid-binding immunoglobulin-like lectins, commonly abbreviated as **Siglecs**, are a family of cell surface proteins within the immunoglobulin superfamily that specifically bind sialic acid-containing glycans[1][4][5]. Siglecs are most prominently expressed on immune cells, such as macrophages, dendritic cells, B cells, natural killer cells, and other leukocytes, where they function as either inhibitory or, less commonly, activating receptors[1][4][8]. They participate in the regulation of immune activation, discrimination between self and non-self, modulation of inflammation, and immune responses in contexts such as infection, autoimmunity, cardiovascular, and neurodegenerative disease[7][8][6]. Individual Siglecs, such as CD22 (Siglec-2), CD33 (Siglec-3), and Sialoadhesin (Siglec-1/CD169), have distinct tissue distributions and functional roles. Siglecs influence signaling processes through intracellular motifs including immunoreceptor tyrosine-based inhibitory motifs (ITIMs) or association with adaptor molecules like DAP12[4][5]. There are at least 14 known human Siglecs, divided into evolutionarily conserved and CD33-related subgroups, with drug development efforts focusing on selected Siglec family members for cancer and autoimmune disease[8].

Other names

Sialic acid-binding immunoglobulin-type lectinSiglecI-type lectin (subfamily: Siglecs)Sialoadhesin (for Siglec-1)CD22 (for Siglec-2)CD33 (for Siglec-3)Myelin-associated glycoprotein (MAG, for Siglec-4)CD33-related Siglecs (for subgroup members)CD169 (for Siglec-1)

Antibody-based blockade or agonism Immune cell modulation via inhibitory or activating signaling Enhancing antigen presentation Inhibiting immune cell activation (for inhibitory Siglecs with ITIMs) Promoting immune destruction of target cells by unmasking/tunability