Glycoimmunology: Decoding the Sugar Code in Immunity, Inflammation, and Therapy

Glycosylation lies at the heart of immune regulation. Glycans and glycan-binding proteins, including Siglecs, galectins, C-type lectins, and DC-SIGN, are central regulators of innate and adaptive immunity, shaping how immune cells sense, communicate, and respond to pathological signals. At the same time, the metabolic state of immune cells profoundly influences glycan biosynthesis: nutrient availability steers the hexosamine biosynthetic pathway and related metabolic routes, determining the glycan composition of cell-surface proteins and lipids. This reciprocal relationship between glycosylation and immune metabolism represents a rapidly advancing frontier at the intersection of immunology, glycobiology, and translational medicine.Recent advances have illuminated the scope and complexity of glyco-immune coupling. Shifts in glucose, glutamine, and lipid metabolism dynamically reprogram glycosylation patterns, affecting signaling through Siglec–sialic acid and galectin–glycan networks, modulating immune checkpoints, and tuning cell–cell interactions. Lectin receptors, including C-type lectins and DC-SIGN, govern innate pattern recognition, pathogen sensing, and dendritic cell function, while O-GlcNAcylation links nutrient flux to gene expression and inflammatory signaling. Glycan remodeling through sialylation, fucosylation, and glycan branching controls immune cell trafficking, receptor stability, cytokine responses, and effector functions across diverse disease contexts, from infection and autoimmunity to allergy, chronic inflammation, tissue repair, and cancer. Novel single-cell and spatial glycomics, metabolomics–glycomics integration, and CRISPR-based functional screening approaches now offer unprecedented resolution for mapping these pathways, yet translation into clinical tools and targeted therapies remains an open frontier.This Research Topic aims to consolidate current understanding and catalyze future discovery at the interface of glycosylation and immune regulation. We seek to address the reciprocal control of immune metabolism and glycosylation, mechanisms of glycan-mediated immune checkpoint modulation, the potential of glycoengineering to reshape immune cell surfaces and receptor–ligand interactions, and the development of glycan-based biomarkers and therapeutics. By fostering interdisciplinary dialogue across basic and translational research, this initiative bridges mechanistic insights with clinical applications for better management of immune-mediated diseases.The scope of this Research Topic spans mechanistic and translational dimensions, encompassing glycosylation-driven immune regulation in inflammation and related pathologies. Studies integrating basic science and clinical relevance are especially welcome. We invite original research, reviews, methods, and perspectives addressing, but not limited to, the following themes:- Glycan- and lectin-mediated regulation of innate and adaptive immune responses, including roles of Siglecs, galectins, C-type lectins, DC-SIGN, and related glycan-binding receptors- Glycosylation-driven control of immune-cell activation, differentiation, trafficking, cytokine responses, immune checkpoints, and effector functions- Links between defined glycan motifs, glycosylation pathways, and specific immunological outcomes in infection, autoimmunity, allergy, chronic inflammation, tissue repair, and cancer- Interactions between immune metabolism and glycosylation, including nutrient-sensing pathways, hexosamine biosynthesis, - O-GlcNAcylation, and glycan remodeling during immune activation- Glycoengineering strategies to modulate immune responses, remodel immune-cell surfaces, alter receptor–ligand interactions, or tune inflammatory and immunosuppressive pathways- Glycan-based therapeutic approaches, including glycomimetics, glycan-based vaccines and adjuvants, lectin/Siglec-targeted therapies, glyco-enzyme modulation, and glycan-informed immunotherapies- Glycosylation-based biomarkers for immune disease stratification, diagnosis, disease monitoring, and prediction of therapeutic responseInterdisciplinary submissions bridging basic mechanisms with disease models and therapeutic development are strongly encouraged, including single-cell and spatial glycomics/glycoproteomics, integrated metabolomics–glycomics workflows, and CRISPR-based functional screening of glycoenzymes and transporters. Topic editors: Md Mohosin Rana, Koichi Furukawa Source: https://www.frontiersin.org/research-topics/83008/glycoimmunology-decoding-the-sugar-code-in-immunity-inflammation-and-therapy