Macrophage Siglec Receptor (Siglec)

Siglecs (Sialic acid-binding immunoglobulin-like lectins) are a family of cell surface receptors predominantly expressed on immune cells, including macrophages. These receptors recognize sialic acid-containing glycans and play crucial roles in modulating immune responses, particularly by mediating immune resolution and maintaining homeostasis. Macrophage-expressed Siglecs act as glycoimmune checkpoints. They typically contain cytosolic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). Upon ligand binding (to sialoglycans), they recruit phosphatases such as SHP1/2 to dampen activation signals, leading to reduced production of pro-inflammatory cytokines and increased anti-inflammatory cytokines like IL-10, helping resolve inflammation or maintain an immunosuppressive environment. Targeting the interaction between sialoglycans and macrophage-expressed Siglecs is being explored for cancer immunotherapy.

Other names

Sialic acid-binding immunoglobulin-like lectinsSialoadhesinCD33Siglec-1Siglec-3Siglec-5Siglec-GSiglec-7Siglec-9

Blocking Siglec receptors or cleaving sialoglycans via sialidases to repolarize macrophages and enhance anti-tumor immunity.