Sialic acid-binding immunoglobulin-like lectin E (Siglec-E) (Siglec-E)

Sialic acid-binding immunoglobulin-like lectin E (Siglec-E) is a cell-surface inhibitory receptor primarily expressed on myeloid cells, including neutrophils, macrophages, and dendritic cells (UniProt Q91Y57). As a member of the CD33-related Siglec family, it functions as an I-type lectin that recognizes sialic acid-containing glycans, which are often referred to as self-associated molecular patterns (SAMPs) (PubMed: 25108027). Upon binding to these ligands, Siglec-E recruits tyrosine phosphatases SHP-1 and SHP-2 via its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs), leading to the suppression of activating signaling pathways (PubMed: 30655315). This mechanism is crucial for maintaining immune homeostasis and preventing excessive inflammatory damage, particularly in the lungs and during systemic infections like sepsis. In oncology, the Siglec-E/Siglec-9 axis is recognized as a glyco-immune checkpoint; tumor cells often exhibit hypersialylation to engage these receptors and evade immune destruction (Palleon Pharmaceuticals). Therapeutic strategies currently under investigation include sialidase-antibody conjugates, such as E-602, which strip sialic acids from the tumor surface to disrupt Siglec-E/9 mediated immunosuppression. By removing the glycan ligands, these therapies aim to restore the ability of the immune system to recognize and attack malignant cells.

Other names

SigleceCD33L2CD33-like 2Sialic acid-binding Ig-like lectin E

Inhibition of immune cell activation through recruitment of SHP-1 and SHP-2 phosphatases to immunoreceptor tyrosine-based inhibitory motifs (ITIMs) upon binding to sialic acid-containing glycans (PubMed: 30655315).