Volume 77, March 2025, 101925Author links open overlay panel, , , Highlights•

Siglec-ligand and expression table.

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Siglecs in innate and adaptive immunity.

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The roles of Siglecs in the central nervous system.

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Contributions of Siglecs in the fetal maternal interface.

Abstract

Cell surface complex carbohydrates, known as glycans, are positioned to be the first point of contact between two cells. Indeed, interactions between glycans with glycan-binding can modulate cell-cell interactions. This concept is particularly relevant for immune cells, which use an array of glycan-binding proteins to help in the process of differentiating ‘self’ from ‘non-self’. This is exemplified by the sialic acid-binding immunoglobulin-type lectins (Siglecs), which recognize sialic acid. Given that sialic acid is relatively unique to vertebrates, immune cells leverage Siglecs to recognize sialic acid as a marker of ‘self’. Siglecs serve many biological roles, with most of these functions regulated through interactions with their sialoglycan ligands. In this review, we provide a comprehensive update on the ligands of Siglecs and how Siglec-sialoglycan interactions help regulate immune cells in the adaptive and innate immune system.

AbbreviationsITAM

immunoreceptor tyrosine-based activation motif

Fc

fragment crystallizable

CMAH

cytidine monophospho-N-acetylneuraminic acid hydroxylase

GCBCs

germinal center B cells

CLL

chronic lymphocytic leukemia

CIRP

cold-inducible RNA-binding protein

SLE

systemic lupus erythematosus

TILs

tumor-infiltrating lymphocytes

COPD

chronic obstructive pulmonary disease

HUVEC-C

human umbilical vein endothelial cells

MAECs

mouse aortic endothelial cells

PDCs

plasmacytoid dendritic cells

MCMV

murine cytomegalovirus

LCMV

lymphocytic choriomeningitis virus

VZV

varicella-zoster virus

Fn

fusobacterium nucleatum

HIV

human immunodeficiency virus

SARS-CoV-2

severe acute respiratory syndrome coronavirus 2

CNS

central nervous system

EAE

experimental autoimmune encephalomyelitis

SNP

single nucleotide polymorphism

RPTPζ

receptor protein tyrosine phosphatase zeta

Siglec

sialic-acid-binding immunoglobulin-like lectins

GBPs

glycan binding proteins

EVs

extracellular vesicles

ITIM

immunoreceptor tyrosine-based inhibitory motif

DAP12

DNAX activation protein of 12 kDa

ERK

extracellular signal-regulated kinase

ITSM

immunoreceptor tyrosine-based switch motifs

DMBT1

deleted in malignant brain tumors 1

Keywords

Siglec

glycan

sialic acid

immunoregulatory

carbohydrate

© 2024 The Author(s). Published by Elsevier Ltd.