Immunometabolic Regulation of Dendritic Cell Function

Dendritic cells occupy a pivotal role at the nexus of metabolism and immune regulation, employing distinct bioenergetic programmes to calibrate antigen uptake, processing and presentation. In their immature state, dendritic cells rely predominantly on mitochondrial oxidative phosphorylation to support tolerance and tissue homeostasis. Upon sensing danger signals, a swift metabolic switch towards aerobic glycolysis furnishes rapid ATP and biosynthetic precursors necessary for upregulation of costimulatory molecules, cytokine secretion and migration to lymphoid organs. Nutrient availability and metabolite flux—encompassing glucose, fatty acids and amino acids—further shape dendritic cell subset differentiation and functional plasticity. Epigenetic modifications such as histone acetylation, driven by intermediary metabolites, reinforce transcriptional programmes that underpin antigen‐presenting capacity. Conversely, metabolic stressors, including hyperglycaemia or tumour‐derived lactate, can impair dendritic cell maturation and T cell priming, with profound implications for antiviral defence, cancer immunity and chronic inflammation. Understanding these interconnected pathways offers new avenues for therapeutic manipulation of dendritic cell function in vaccination, cancer immunotherapy and the management of metabolic disorders.

Research from Nature Portfolio

Recent studies have revealed that elevated blood glucose in diabetic models reshapes chromatin landscapes in lung dendritic cells, driven by enhanced conversion of glucose to acetyl‐CoA and subsequent histone acetylation. This epigenetic reprogramming diminishes expression of key antigen‐presentation genes, impairs costimulatory molecule display and delays viral clearance, yet can be reversed by pharmacological modulation of histone acetylation or glycaemic control. In parallel, analysis of dendritic cell vaccines in melanoma patients has identified distinct immunometabolic signatures correlating with overall survival. A shift from oxidative phosphorylation to glycolysis, accompanied by upregulation of monocarboxylate transporter-1 and increased lactate secretion, was linked to enhanced immunostimulatory potential, suggesting that pre-vaccination metabolic profiling may inform personalised vaccine design. Foundational work on nutrient competition has further elucidated how glucose availability within immune microenvironments dictates dendritic cell activation thresholds and subsequent T cell priming, highlighting nutrient uptake as a rheostat for adaptive immunity.

Immunometabolic Regulation of Dendritic Cell Function publication trend

The graph below shows the total number of articles in immunometabolic regulation of dendritic cell function across all publications each year (not limited to Nature Index journals).

Technical terms

Glycolysis: The metabolic pathway that converts glucose to pyruvate, generating ATP and metabolic intermediates for biosynthesis.

Oxidative phosphorylation: Mitochondrial process that produces ATP through electron transport and proton gradient across the inner membrane.

mTOR: Mechanistic target of rapamycin, a serine/threonine kinase that senses nutrient availability and regulates cell growth and metabolism.

AMPK: AMP-activated protein kinase, a cellular energy sensor that promotes catabolic pathways when cellular ATP is low.

Histone acetylation: Addition of acetyl groups to histone proteins, leading to a more open chromatin conformation and active gene transcription.

Antigen presentation: Display of peptide fragments bound to major histocompatibility complex molecules on the cell surface for recognition by T cells.

References

1. Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes. Nature (2023).
2. Immuno-metabolic dendritic cell vaccine signatures associate with overall survival in vaccinated melanoma patients. Nature Communications (2023).
3. Competition for nutrients and its role in controlling immune responses. Nature Communications (2019).
4. Dynamic glycolytic reprogramming effects on dendritic cells in pancreatic ductal adenocarcinoma. Journal of Experimental & Clinical Cancer Research (2024).
5. Polyphenols: immunonutrients tipping the balance of immunometabolism in chronic diseases. Frontiers in Immunology (2024).
6. Leonurine promotes the maturation of healthy donors and multiple myeloma patients derived-dendritic cells via the regulation on arachidonic acid metabolism. Frontiers in Pharmacology (2023).