Siglec-11 Activators

Siglec-11, or Sialic acid-binding Ig-like lectin 11, is a protein that in humans is encoded by the SIGLEC11 gene. Siglecs are a family of cell surface receptors that are primarily found on immune cells and are known for binding sialic acids, a family of sugar molecules present on various glycoproteins and glycolipids on cell surfaces. This binding activity is important for cell-cell communication and can modulate immune responses.Siglec-11 has a distinct preference for certain sialic acid linkages, which can influence its role in the immune system. Structurally, like other Siglecs, Siglec-11 comprises an N-terminal V-set immunoglobulin-like domain that is responsible for sialic acid binding, followed by varying numbers of C2-set immunoglobulin-like domains, and a transmembrane region with a cytoplasmic tail that contains signaling motifs.

The cytoplasmic domain of Siglec-11 bears an immunoreceptor tyrosine-based inhibitory motif (ITIM) and, in some cases, an immunoreceptor tyrosine-based switch motif (ITSM). These motifs are important for transmitting inhibitory signals to the interior of the cell upon receptor engagement, generally leading to the suppression of immune cell activation. Thus, Siglec-11 is thought to play a role in inhibiting inappropriate or overactive immune responses, maintaining immune homeostasis.In humans, Siglec-11 is expressed on macrophages and other myeloid cells and is notable for its expression in the brain, particularly in microglia, the resident immune cells of the central nervous system (CNS). Its expression in the CNS is of significant interest, as it may have implications for neuroinflammation and the immune privilege of the brain.