The Role of Siglecs in Immune Signaling Regulation and Immune Pathology / 中国生物化学与分子生物学报

Sialic acid-binding immunoglobulin-like lectins (Siglecs) are members of the immunoglobulin superfamily expressed in most white blood cells of the immune system. The Siglec is a kind of transmembrane proteins that can recognize sialic acid-containing ligands, and it is the most important subgroup of type I lectin. All Siglecs contain at least three domains, including the V-set Ig domain, C2-set Ig domain and transmembrane domain. Some Siglecs contain immune receptor tyrosine-based inhibitory motifs (ITIMs), which are used to transmit inhibitory signals and play an inhibitory role. There are also some Siglecs that do not contain intracellular domains, and they can transmit activation signals through basic amino acids in transmembrane domains to play an activation role. Siglecs not only participate in the regulation of activation, proliferation and apoptosis of immune cells, but also help the immune system to distinguish itself from non-itself by recognizing glycan ligands containing sialic acid. In recent years, studies have shown that Siglecs, as an immune checkpoint, play an important role in the immune regulation in human diseases such as cancer, asthma, allergy, Alzheimer’s disease and autoimmune diseases, and it has received extensive attention. Enhancing or blocking the interaction of sialic acid with Siglecs is an effective strategy for the treatment of cancer, infection, and other diseases. In this review, we describe the classification of Siglecs, their expression in different immune cells and their role in the regulation of immune cell signaling. Emphasis was placed on the role of Siglecs in disease and methods of targeting Siglecs for the treatment of human diseases.

Role of Siglecs and their ligands in the establishment of immune tolerance at maternal-fetal interface / 中华微生物学和免疫学杂志

Embryo is regarded as a semi-allograft for carrying paternal genetic information. It can escape the attack from maternal immune system and successfully implant into the uterus, which mainly relies on the establishment of immune tolerance at the maternal-fetal interface. The maternal-fetal interface is the basis for the connection and material exchange between the mother and fetus. The mechanisms of immune re-sponses at this interface are the key to the maintenance of normal pregnancy. Immunomodulatory molecules expressed at the maternal-fetal interface are vital for immune tolerance. Studies have shown that sialicacid-binding immunoglobulin-like lectins (Siglecs) are abundantly expressed at the maternal-fetal interface and play an important role in immune regulation. Siglecs are important members of the typeⅠimmunoglobulin-like superfamily. By binding with the sialic acid residues on the side chains of glycoproteins or glycolipids, Siglecs involve in immune regulation, the activation and proliferation of immune cells and immune cell-medi-ated physiological and pathological processes. Present research on the expression of Siglecs in the maternal-fetal interface is mainly focused on Siglec-6 and Siglec-10, while other Siglecs are less studied. Siglecs, such as Siglec-6 and Siglec-10, might involve in the regulation of immune tolerance at the maternal-fetal in-terface through binding to different ligands. This article briefly reviewed the expression of Siglecs and their ligands at the maternal-fetal interface and their roles in immune tolerance.

Sialic acids siglec interaction A unique strategy to circumvent innate immune response by pathogens.

Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host’s immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.

Functions of Siglecs in Allergic Inflammation / 소아알레르기및호흡기학회지

Siglecs are sialic acid binding Ig-like lectins, subset of the immunoglobulin superfamily. They are characterized by a homologous N-terminal V-set Ig-like domain and C2 set Ig-like domains. N-terminal domains have sialic acid binding activity. In humans, 11 Siglecs have been described sialoadhesin(Siglec-1), CD22(Siglec-2), CD33(Siglec-3), MAG(Siglec-4), more recently described CD33-related Siglecs(Siglec 5-11). Siglecs express most signal via immunoreceptor tyrosine-based inhibition motif(ITIM) cytoplasmic domains. The cytoplasmic tails of all Siglecs except sialoadhesin have one or more tyrosine residues within potential signaling motifs. Inhibitory function of other Siglecs such as Siglec-7 or Siglec-9 was shown in RBL-2H3 cells. Co-crosslinking of Siglec-7 or Siglec-9 and Fc epsilon R1 substantially reduced the serotonin release of RBL-7 and RBL-9 cells. Siglec-8 is expressed on human eosinophils, mast cells and basophils. Siglec-8 has two tyrosine motifs, a proximal motif and a distal motif. They have some inhibitory functions in immune system. We have observed that Siglec-8 is able to inhibit the IgE receptor-mediated beta-hexosaminidase release of RBL-2H3 cells following co-crosslinking. Co-crosslinking of Siglec-8 and Fc epsilon R1 reduced the hexosaminidase release of RBL-2H3 cells. These results show that Siglec-8 is as potent as Siglec-7 and Siglec-9 in delivering inhibitory signals to RBL-2H3 cells. Siglec-8 should be a new member of the inhibitory receptor superfamily and the membrane-proximal ITIM is essential for the inhibitory function of Siglec-8 molecules. Although these molecules present specific marker for the allergic cell types, more work is needed to understand the signaling mechanism and the role in various disease processes.