Glycosylation and Acylation: Important Regulators of Immune Cell Fate Decisions

Dissecting the determinants of immune cell fate is a central challenge in immunology and is important for understanding cell differentiation, disease diagnosis, and therapy. Post-translational modifications (PTMs) of proteins are chemical modifications of amino acids involving the addition or removal of specific groups. As molecular gatekeepers of immune cell fate, PTMs affect immune function mainly through the regulation of important life processes such as immune cell growth, proliferation, differentiation, activation, and apoptosis. Among PTMs, glycosylation and acylation have emerged as critical regulatory mechanisms governing immune homeostasis. Through precise structural alterations of immune-related proteins and receptors, glycosylation shapes antigen recognition, cytokine signaling, and intercellular communication, while acylation regulates signal transduction and epigenetic modifications in both innate and adaptive immunity. These modifications are involved in the regulation of a wide range of biological processes and are intricately associated with the pathogenesis of many diseases, especially immune diseases. Therefore, this paper reviews the functions and mechanisms of glycosylation and acylation in regulating innate and acquired immunity, to provide new insights into the role of PTMs in disease pathogenesis and potential targeted therapies.