Functional and Metabolic Heterogeneity of Dendritic Cells in Self‐Tolerance and Autoimmunity

Dendritic cells (DCs) demonstrate remarkable functional and metabolic heterogeneity that governs the balance between immune tolerance and autoimmune pathogenesis. Under homeostatic conditions, tolerogenic DC subsets maintain immunological equilibrium through distinct metabolic programs and the production of immunoregulatory metabolites, promoting T cell anergy and regulatory T cell (Treg) differentiation. In contrast, autoimmune conditions trigger pathogenic metabolic rewiring, shifting DCs toward glycolysis and enhanced lipid synthesis, which drives DC hyperactivation and breakdown of self‐tolerance. This metabolic reprogramming is coordinately regulated by external microenvironmental cues and internal signaling pathways, leading to heterogeneous DC responses in diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and psoriasis. Targeting metabolic regulators offers promising therapeutic strategies to restore immune tolerance and prevent harmful autoimmunity and inflammation. The review highlights the intricate interplay between DC metabolism and function, emphasizing how metabolic heterogeneity underpins their dual roles in immune regulation and autoimmunity. Future exploration of subset‐specific metabolic preferences and spatiotemporal metabolic dynamics will facilitate the development of precision immunotherapies for autoimmune diseases.

• Publication year

  2025

• Venue

  Immunological Reviews

• Publication date

  2025-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/imr.70068PMID 41219689
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Unraveling porcine dendritic-cell diversity: welcome tDC and DC3

  2025cited by this paper
• Cholesterol mobilization regulates dendritic cell maturation and the immunogenic response to cancer

  2025influential reference
• Mechanosensing regulates pDC activation in the skin through NRF2 activation.

  2025cited by this paper
• RORγt-expressing dendritic cells are functionally versatile and evolutionarily conserved antigen-presenting cells

  2025cited by this paper
• Thymic DC2 are heterogenous and include a novel population of transitional dendritic cells

  2025cited by this paper
• Unraveling dendritic-cell diversity in blood of pigs: welcome tDC and DC3

  2025cited by this paper
• Spectral cytometry of rheumatoid arthritis patients implicates myeloid dendritic cells and granular HLA-DR+CD15+CD16+ cells in pro-inflammatory antigen presentation

  2025cited by this paper
• Rorγt-positive dendritic cells are required for the induction of peripheral regulatory T cells in response to oral antigens.

  2025cited by this paper
• Nuclear adenine activates hnRNPA2B1 to enhance antibacterial innate immunity.

  2025cited by this paper
• Gut bacterial L-lysine alters metabolism and histone methylation to drive dendritic cell tolerance.

  2025cited by this paper
• STAT5 and STAT3 balance shapes dendritic cell function and tumour immunity

  2025cited by this paper
• Rescuing dendritic cell interstitial motility sustains antitumour immunity.

  2025cited by this paper
• Metabolic Reprogramming of Neural Stem Cells by Chiral Nanofiber for Spinal Cord Injury

  2025cited by this paper
• Mitochondrial DNA oxidation propagates autoimmunity by enabling plasmacytoid dendritic cells to induce TFH differentiation

  2025cited by this paper
• Plasmacytoid dendritic cells alleviate allergic asthma via airway epithelial cells-dependent thymosin β4 expression.

  2025cited by this paper
• The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity.

  2024cited by this paper
• Single-cell spatiotemporal analysis reveals alveolar dendritic cell–T cell immunity hubs defending against pulmonary infection

  2024cited by this paper
• Dubosiella newyorkensis modulates immune tolerance in colitis via the L-lysine-activated AhR-IDO1-Kyn pathway

  2024cited by this paper
• Striking a balance: new perspectives on homeostatic dendritic cell maturation

  2024influential reference
• Altered X-chromosome inactivation of the TLR7/8 locus and heterogeneity of pDCs in systemic sclerosis

  2024cited by this paper
• Novel AHR ligand AGT-5 ameliorates type 1 diabetes in mice through regulatory cell activation in the early phase of the disease

  2024cited by this paper
• NRF2 Plays a Crucial Role in the Tolerogenic Effect of Ethyl Pyruvate on Dendritic Cells

  2024cited by this paper
• AMPK activation induces RALDH+ tolerogenic dendritic cells by rewiring glucose and lipid metabolism

  2024cited by this paper
• Single-cell spatiotemporal analysis of the lungs reveals Slamf9+ macrophages involved in viral clearance and inflammation resolution

  2024cited by this paper
• Farnesyl pyrophosphate potentiates dendritic cell migration in autoimmunity through mitochondrial remodelling

  2024influential reference
• Long-chain acyl-CoA synthetase 4-mediated mitochondrial fatty acid metabolism and dendritic cell antigen presentation

  2024cited by this paper
• Single-cell profiling reveals kidney CD163+ dendritic cell participation in human lupus nephritis

  2024cited by this paper
• Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity

  2024cited by this paper
• Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis.

  2024influential reference
• Conversion of dendritic cells into tolerogenic or inflammatory cells depends on the activation threshold and kinetics of the mTOR signaling pathway

  2024cited by this paper
• Type I interferon pathway in pediatric systemic lupus erythematosus

  2024cited by this paper
• Patterning of the cell cortex by Rho GTPases

  2024cited by this paper
• Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity.

  2024cited by this paper
• Universal recording of immune cell interactions in vivo

  2024cited by this paper
• Identification and experimental validation of genes associated with programmed cell death in dendritic cells of the thyroid tissue in Hashimoto's thyroiditis.

  2024cited by this paper
• Differences in IDO1+ dendritic cells and soluble CTLA-4 are associated with differential clinical responses to methotrexate treatment in rheumatoid arthritis

  2024cited by this paper
• Stat5b/Ezh2 axis governs high PD-L1 expressing tolerogenic dendritic cell subset in autoimmune diabetes.

  2024cited by this paper
• LRH‐1/NR5A2 targets mitochondrial dynamics to reprogram type 1 diabetes macrophages and dendritic cells into an immune tolerance phenotype

  2024cited by this paper
• Formyl peptide receptor 2 regulates dendritic cell metabolism and Th17 cell differentiation during neuroinflammation

  2024cited by this paper
• Nicotinamide Suppresses Hyperactivation of Dendritic Cells to Control Autoimmune Disease through PARP Dependent Signaling

  2024cited by this paper
• Single-cell transcriptomic analysis identifies infiltrating plasmacytoid dendritic cells in psoriasis epidermis.

  2024cited by this paper
• A positive cytokine/chemokine feedback loop establishes plasmacytoid DC–driven autoimmune pancreatitis in IgG4-related disease

  2024cited by this paper
• Multi-omic analysis revealed the immunological patterns and diagnostic value of exhausted T cell-derived PTTG1 in patients with psoriasis.

  2024cited by this paper
• Metabolic enzyme Suclg2 maintains tolerogenicity of regulatory dendritic cells diffDCs by suppressing Lactb succinylation.

  2023cited by this paper
• Lipid metabolism in dendritic cell biology

  2023cited by this paper
• LXR signaling controls homeostatic dendritic cell maturation

  2023cited by this paper
• Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis

  2023cited by this paper
• AXL+SIGLEC6+ dendritic cells in cerebrospinal fluid and brain tissues of patients with autoimmune inflammatory demyelinating disease of CNS.

  2023cited by this paper
• The role of dendritic cells and their immunometabolism in rheumatoid arthritis

  2023cited by this paper
• Sitagliptin Induces Tolerogenic Human Dendritic Cells

  2023cited by this paper
• Lung dendritic-cell metabolism underlies susceptibility to viral infection in diabetes

  2023cited by this paper
• Reactive oxygen species (ROS) scavenging biomaterials for anti-inflammatory diseases: from mechanism to therapy

  2023cited by this paper
• Effector memory T cells induce innate inflammation by triggering DNA damage and a non-canonical STING pathway in dendritic cells

  2023cited by this paper
• Lactate limits CNS autoimmunity by stabilizing HIF-1α in dendritic cells

  2023influential reference
• Immunomodulation by subcutaneously injected methacrylic acid-based hydrogels and tolerogenic dendritic cells in a mouse model of autoimmune diabetes.

  2023cited by this paper
• Myo9b mutations are associated with altered dendritic cell functions and increased susceptibility to autoimmune diabetes onset

  2023cited by this paper
• Life and death of tolerogenic dendritic cells.

  2023cited by this paper
• Tr1 cell-mediated protection against autoimmune disease by intranasal administration of a fusion protein targeting cDC1 cells

  2023cited by this paper
• Lactobacillus johnsonii N6.2 phospholipids induce immature-like dendritic cells with a migratory-regulatory-like transcriptional signature

  2023cited by this paper
• Stem-like CD4+ T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis

  2023cited by this paper
• Distinct metabolic states guide maturation of inflammatory and tolerogenic dendritic cells

  2022influential reference
• Indoleamine 2,3-dioxygenase 1 activation in mature cDC1 promotes tolerogenic education of inflammatory cDC2 via metabolic communication

  2022cited by this paper
• Chronic activation of pDCs in autoimmunity is linked to dysregulated ER stress and metabolic responses

  2022influential reference
• Single-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus

  2022cited by this paper
• Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in Type 1 Diabetes

  2022cited by this paper
• Dendritic cells in systemic lupus erythematosus: From pathogenesis to therapeutic applications.

  2022cited by this paper
• Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis

  2022cited by this paper
• High-Fat Diet–Induced Obesity Alters Dendritic Cell Homeostasis by Enhancing Mitochondrial Fatty Acid Oxidation

  2022cited by this paper
• Type 1 Diabetes Mellitus

  2022cited by this paper
• A purine metabolic checkpoint that prevents autoimmunity and autoinflammation

  2022cited by this paper
• Dendritic Cells and Macrophages in the Pathogenesis of Psoriasis

  2022cited by this paper
• Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function

  2022cited by this paper
• Classification of human chronic inflammatory skin disease based on single-cell immune profiling

  2022cited by this paper
• Elevations in blood glucose before and after the appearance of islet autoantibodies in children

  2022cited by this paper
• N-Acylethanolamine acid amidase (NAAA) exacerbates psoriasis inflammation by enhancing dendritic cell (DCs) maturation.

  2022cited by this paper
• The epidermal immune microenvironment plays a dominant role in psoriasis development, as revealed by mass cytometry

  2022cited by this paper
• Glycolysis in Innate Immune Cells Contributes to Autoimmunity

  2022cited by this paper
• Vitamin D receptor, STAT3, and TET2 cooperate to establish tolerogenesis.

  2022cited by this paper
• Lithocholic acid inhibits dendritic cell activation by reducing intracellular glutathione via TGR5 signaling

  2022cited by this paper
• Aqueous extract of Passiflora alata leaves modulates in vitro the indoleamine 2,3-dioxygenase (IDO) and CD86 expression in bone marrow-derived professional antigen-presenting cells polarizing NOD mice T cells to a Treg profile.

  2022cited by this paper
• Phosphatidylserine-mediated oral tolerance.

  2022cited by this paper
• Mouse phospholipid phosphatase 6 regulates dendritic cell cholesterol, macropinocytosis, and allergen sensitization

  2022cited by this paper
• Cholesterol accumulation on dendritic cells reverses chronic hepatitis B virus infection-induced dysfunction

  2022cited by this paper
• Single-cell transcriptome profiling of the immune space-time landscape reveals dendritic cell regulatory program in polymicrobial sepsis

  2022cited by this paper
• NCoR1 controls immune tolerance in conventional dendritic cells by fine-tuning glycolysis and fatty acid oxidation

  2022cited by this paper
• Targeting SLC7A11 improves efferocytosis by dendritic cells and wound healing in diabetes

  2022cited by this paper
• Redox regulation of immunity and the role of small molecular weight thiols

  2021cited by this paper
• Inhibition of glycolysis in the presence of antigen generates suppressive antigen-specific responses and restrains rheumatoid arthritis in mice.

  2021cited by this paper
• Remodeling of the Lymph Node High Endothelial Venules Reflects Tumor Invasiveness in Breast Cancer and is Associated with Dysregulation of Perivascular Stromal Cells

  2021cited by this paper
• Evolving concepts in NAD+ metabolism.

  2021cited by this paper
• Investigation of Fascin1, a Marker of Mature Dendritic Cells, Reveals a New Role for IL-6 Signaling in CCR7-Mediated Chemotaxis

  2021cited by this paper
• Adenosine and inflammation: it's time to (re)solve the problem.

  2021cited by this paper
• DNMT1 Deficiency Impacts on Plasmacytoid Dendritic Cells in Homeostasis and Autoimmune Disease

  2021cited by this paper
• Plasmacytoid dendritic cell activation is dependent on coordinated expression of distinct amino acid transporters.

  2021cited by this paper
• Hypoxia promotes the tolerogenic phenotype of plasmacytoid dendritic cells in head and neck squamous cell carcinoma

  2021cited by this paper
• Single-cell analysis of human skin identifies CD14+ type 3 dendritic cells co-producing IL1B and IL23A in psoriasis

  2021cited by this paper
• Gut microbiota-mediated secondary bile acids regulate dendritic cells to attenuate autoimmune uveitis through TGR5 signaling.

  2021cited by this paper
• Tertiary lymphoid structures critical for prognosis in endometrial cancer patients

  2021cited by this paper
• Tumour fatty acid metabolism in the context of therapy resistance and obesity

  2021cited by this paper
• Dendritic cell migration in inflammation and immunity

  2021cited by this paper

• Gene expression profiling of dendritic cell tolerance dysfunction in women with Systemic lupus erythematosus

  2025cites this paper