Monosaccharides as Regulators of T Cell Function: Mechanisms and Therapeutic Potential

Carbohydrates and their constituent monosaccharides have historically been viewed as metabolic substrates that provide cellular energy. However, recent evidence demonstrates that monosaccharides can also function as bioactive signaling molecules that affect immune responses through cellular metabolic reprogramming, post-translational protein glycosylation, receptor complex modulation, and transcriptional regulation of immune cell differentiation. These discoveries have given rise to the emerging concept of glyconutraceuticals, bioactive carbohydrates with therapeutic potential. This review discusses current evidence for the immunomodulatory properties of glucose, D-mannose, sialic acid, L-fucose, galactose, N-acetylglucosamine, D-xylose, and L/D-arabinose, with particular emphasis on their mechanisms of action in T cell activation, subset differentiation, metabolic reprogramming, and anti-tumor cytotoxicity. The context-dependent and often opposing effects of individual monosaccharides across T cell subsets underscore the complexity of immunomodulation by glyconutrients.