Sialic acids and autoimmune disease

Abstract

summary An important underlying mechanism that contributes to autoimmunity is the loss of inhibitory signaling in the immune system. Sialic acid-recognizing Ig superfamily lectins or Siglecs are a family of cell surface proteins largely expressed in hematopoietic cells. The majority of Siglecs are inhibitory receptors expressed in immune cells that bind to sialic acid containing ligands and recruit SH2-domain containing tyrosine phosphatases to their cytoplasmic tails. They deliver inhibitory signals that can contribute to the constraining of immune cells and thus protect the host from autoimmunity. The inhibitory functions of CD22/Siglec-2 and Siglec-G and their contributions to tolerance and autoimmunity, primarily in the B lymphocyte context, are considered in some detail in this review. The relevance to autoimmunity and unregulated inflammation of modified sialic acids, enzymes that modify sialic acid, and other sialic acid binding proteins are also reviewed.

Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain

“…Given that these mice generate altered forms of sialic acid that are not recognized by key regulatory Siglecs expressed on B cells (such as CD22/Siglec-2 and Siglec-G), the defects in B cell development observed in these mice were presumed to arise from perturbations in Siglec function(Cariappa et al, 2009; Pillai et al, 2009). In addition, the observed phenotypes were largely compatible with previous studies of Siglec function(Mahajan and Pillai, 2016; Pillai et al, 2009). Notably, both Siae Δex2/Δex2 and Cmah knockout mice were originally generated at UC San Diego and had been backcrossed into a specific commercially-obtained C57BL/6 background for ten generations(Cariappa et al, 2009; Hedlund et al, 2007).…”

Characterisation of the Dynamic Interactions between Complex N‐Glycans and Human CD22

“…In recent years, great attention has been focused on CD22, also known as Siglec‐2, an inhibitory B‐cell‐specific glycoprotein that preferentially recognises α‐(2→6)‐linked sialic acid ligands, thereby preventing dysregulation of tolerance mechanisms, self‐reactivity and autoimmunity . Under physiological conditions, on resting B‐cells, CD22 is “masked” by cis interactions with sialoglycans exposed on the same plasma membrane, resulting in the formation of homo‐oligomers that sequester the CD22 away from the B‐cell receptor (BCR) .…”

Chemical composition of circulating native and desialylated low density lipoprotein: what is the difference?

“…[ [79][80][81][82] In atherosclerosis, decreased sialic acid content in desialylated LDL might result in increased cholesterol intake and inflammation through macrophage and B-cell activation.…”