Immunological and pathological roles of Siglecs: a molecular review

Siglecs are sialic acid-binding immunoglobulin-like receptors that regulate immune responses through inhibitory and activating signaling pathways. By recognizing sialoglycan ligands, they modulate innate and adaptive immunity, and their dysregulation is increasingly linked to diverse human diseases. This review highlights the roles of human Siglecs in disease pathogenesis, including cancer, autoimmune and inflammatory disorders, neurodegeneration, and infections. We summarize key regulatory mechanisms such as transcription factors, microRNAs, and protein interactions and outline major signaling pathways underlying Siglec-mediated immune modulation. At the molecular level, Siglecs signal via ITIM dependent inhibitory pathways SHP-1/SHP-2 or ITAM/DAP12-associated activation SYK/MAPK, maintaining immune homeostasis. Targeting the Siglec glycan axis offers promising therapeutic opportunities.