Abstract
Siglecs are sialic acid-binding immunoglobulin-like lectins. Most Siglecs function as transmembrane receptors mainly expressed on blood cells in a cell type-specific manner. They recognize and bind sialic acids in specific linkages on glycoproteins and glycolipids. Since Sia is a self-molecule, Siglecs play a role in innate immune responses by distinguishing molecules as self or non-self. Increasing evidence supports the involvement of Siglecs in immune signaling representing immune checkpoints able to regulate immune responses in inflammatory diseases as well as cancer. Although further studies are necessary to fully understand the involvement of Siglecs in pathological conditions as well as their interactions with other immune regulators, the development of therapeutic approaches that exploit these molecules represents a tremendous opportunity for future treatments of several human diseases, as demonstrated by their application in several clinical trials. In the present review, we discuss the involvement of Siglecs in the regulation of immune responses, with particular focus on autoimmunity and cancer and the chance to target the sialic acid-Siglec axis as novel treatment strategy.
Highlights
Biology of the Sialic Acid-Sialic Acid-Binding Immunoglobulin-LikeLectin (Siglec) AxisThe membrane of every living cell, in addition to nucleic acids, lipids, and proteins, displays various glycans
Such a role has been demonstrated by the observations that halting the sialic acids (Sias)–Sialic Acid-Binding Immunoglobulin-LikeLectin (Siglec) axis could even cause the breakage of peripheral tolerance and autoimmunity
In this review we analyzed the role of the sialic acid-Siglec interactions in immune mediated diseases and cancer and possible immunomodulatory therapeutic approaches based on Sia–Siglecs axis modulation
Summary
The membrane of every living cell, in addition to nucleic acids, lipids, and proteins, displays various glycans (carbohydrates). In the Golgi apparatus of mammals, 20 rather conserved enzymes defined sialyltransferases attach sialic acids via a diversity of linkages (α2,3, α2,6, and α2,8); this enables cells tocell display on the acell membrane a great variety with of sialoglycans with great structural the membrane great variety of sialoglycans great structural diversity that condiversity that constitute the so-called ‘sialome’. Sias function many of their effects remain to beto fully elucidated [1] Sias both at both mo- at molecular and cellular by interacting with selectins, H, and Sia-binding lecular and cellular level bylevel interacting with selectins, factor H,factor and Sia-binding immuno-immunoglobulin (Ig)-like lectins The (Siglecs). Pathways (Figure 1) [14]
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