O-GlcNAc: a novel regulator of immunometabolism

• Published in: Journal of bioenergetics and biomembranes 2018-06, Vol.50 (3), p.223-229
• Main Authors: Machacek, Miranda, Slawson, Chad, Fields, Patrick E.
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Animal Anatomy; Animal Biochemistry; Autoimmune diseases; Autoimmunity; Biochemistry; Bioorganic Chemistry; CD4 antigen; Cell activation; Chemistry; Chemistry and Materials Science; Eradication; Histology; Immune response; Immune system; Influence functions; Localization; Lymphocytes; Lymphocytes T; Metabolic flux; Metabolic pathways; Metabolism; Mini-Review; Morphology; N-Acetylglucosamine; Organic Chemistry; Pathogenicity; Pathogens; Post-translation; Proteins
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-018-9744-1

The rapidly expanding field of immunometabolism focuses on how metabolism controls the function of immune cells. CD4 + T cells are essential for the adaptive immune response leading to the eradication of specific pathogens. However, when T cells are inappropriately over-active, they can drive autoimmunity, allergic disease, and chronic inflammation. The mechanisms by which metabolic changes influence function in CD4 + T cells are not fully understood. The post-translational protein modification, O-GlcNAc (O-linked β-N-acetylglucosamine), dynamically cycles on and off of intracellular proteins as cells respond to their environment and flux through metabolic pathways changes. As the rate of O-GlcNAc cycling fluctuates, protein function, stability, and/or localization can be affected. Thus, O-GlcNAc is critically poised at the nexus of cellular metabolism and function. This review highlights the intra- and extracellular metabolic factors that influence CD4 + T cell activation and differentiation and how O-GlcNAc regulates these processes. We also propose areas of future research that may illuminate O-GlcNAc’s role in the plasticity and pathogenicity of CD4 + T cells and uncover new potential therapeutic targets.