Abstract
The sialic acid-binding immunoglobulin-type of lectins (Siglecs) are receptors that recognize sialic acid-containing glycans. In the majority of the cases, Siglecs are expressed on immune cells and play a critical role in regulating immune cell signaling. Over the years, it has been shown that the sialic acid-Siglec axis participates in immunological homeostasis, and that any imbalance can trigger different pathologies, such as autoimmune diseases or cancer. For all this, different therapeutics have been developed that bind to Siglecs, either based on antibodies or being smaller molecules. In this review, we briefly introduce the Siglec family and we compile a description of glycan-based molecules and antibody-based therapies (including CAR-T and bispecific antibodies) that have been designed to therapeutically targeting Siglecs.
Highlights
Chemical Glycobiology Laboratory, CIC bioGUNE, Basque Research and Technology Alliance, BRTA, Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain
The sialic acid binding immunoglobulin (Ig)-like lectins (Siglecs) family in humans is composed by 15 members and in general, they are all expressed in immune cells (Figure 1) [1,2]
Siglecs belong to the I-type family of lectins that recognize sialic acid containing glycans through their extracellular domain (ECD)
Summary
The sialic acid binding immunoglobulin (Ig)-like lectins (Siglecs) family in humans is composed by 15 members and in general, they are all expressed in immune cells (Figure 1) [1,2]. Since sialic acids are found on all mammalian cells, Siglecs can help the immune system in distinguishing between self and non-self signals. Recognition of their sialylated ligands by the. Siglecs have found different ways to impart cellular responses Their functions are shaped by the cellular distribution and ligand specificity and vary from enabling cell adhesion. Siglecs can be divided into two groups (classic and CD33/Siglec-3 related) based on sequence similarity and evolutionary conservation. The cell-expression patterns are shown (Mø, macrophages; DC, dendritic cell; B, B cells; MC, mast cells; Schw, Schwann cells; OD, oligodendrocytes; Ocl, osteoclasts; Myp, myeloid progenitor; Mo, monocytes; Mic, microglia; N, neutrophils; Troph, trophoblasts; NK, natural-killer cells; T, T cells; Eo, eosinophils; Ba, basophils; Lum epi, lumen epithelia cells)
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