Glycosylation in Immune Regulation and Inflammatory Diseases

Glycosylation is a fundamental and ubiquitous post-translational modification that involves the enzymatic attachment of carbohydrate structures (glycans) to proteins, lipids, and, most recently discovered, RNAs. It plays a critical role in modulating protein stability, folding, and cellular communication. In recent years, the intricate relationship between glycosylation and the immune system has garnered significant attention. Glycans are essential for the proper function of immune receptors, the regulation of immune cell trafficking, and the fine-tuning of both innate and adaptive immune responses. This review synthesizes current knowledge on the molecular mechanisms by which glycosylation governs immune regulation, with a particular focus on inflammasome activation. We discuss how specific glycan structures, glycosylation patterns, and glycan-binding proteins (lectins such as Siglecs and galectins) modulate inflammatory pathways. Furthermore, we explore the implications of aberrant glycosylation in autoimmune and inflammatory pathologies, including rheumatic diseases, psoriasis, and various cancers. The emerging discovery of glycoRNAs, a novel class of glycosylated small RNAs, is also highlighted for their roles in immune recognition. Finally, we outline promising therapeutic avenues, including glycoengineering of immune cells, targeted inhibition of pathological glycosylation, and the use of glycan microarrays for biomarker discovery in inflammatory diseases and cancer.