Siglec-8 Activators

Siglec-8, or Sialic acid-binding Ig-like lectin 8, is a protein selectively expressed on the surface of eosinophils, mast cells, and, to a lesser extent, basophils, which are immune cells implicated in the pathogenesis of allergic reactions and asthma. As a member of the Siglec family, it specifically recognizes sialic acid motifs on glycoproteins or glycolipids, which are abundant on cell surfaces.

The engagement of Siglec-8 with its ligands leads to the induction of eosinophil apoptosis and the inhibition of mast cell degranulation, thereby attenuating allergic and inflammatory responses. This makes Siglec-8 an attractive target for intervention in allergic diseases. The cross-linking of Siglec-8 on eosinophils triggers cell death, which is a unique feature among Siglecs and highlights its role in regulating eosinophil life span and function.The signaling pathways downstream of Siglec-8 activation involve the recruitment of SH2 domain-containing tyrosine phosphatases, which then modulate various intracellular pathways, leading to changes in cell survival and activation. The expression of Siglec-8 itself is regulated by factors that influence the differentiation and maturation of eosinophils and mast cells, and its expression levels can be indicative of the activation state of these cells.