ArticleNature communications2025
Lactate activates trained immunity by fueling the tricarboxylic acid cycle and regulating histone lactylation.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed.
- Metabolic reprogramming in colorectal cancer: Mechanisms and therapeutic insights.Genes & diseases · 2027Review
- Antifibrotic monocyte activation by nanoparticles resolves murine pulmonary fibrosis.Biomaterials · 2026Article
- Lactate-Mediated Lysine Lactylation in Renal Fibrosis: Current Progress and Challenges.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Trained immunity: An unexplored component of IBD pathogenesis.Inflammatory bowel diseases · 2026Review
- Lactate Metabolism: Separating Correlation From Causation.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Injection site dictates the immune response to a biodegradable polymer and corresponding collagen regeneration.Bioactive materials · 2026Article
- Lactate metabolism and protein lactylation in inflammatory and tumor microenvironments.Molecular biomedicine · 2026Review
- Metabolic-epigenetic rewiring of CCR5Science advances · 2026Article
- LPS and β-Glucan Induce Differential Memory-like Inflammatory Responses with Enhanced Reactivity in Neonatal Neutrophils Compared to Adults.International journal of molecular sciences · 2026Article
- Safety, tolerability, and gastrointestinal effect of a Bifidobacterium-based synergistic synbiotic in infants and toddlers.Pediatric research · 2026Article
- Innate immunity: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A Lactate-H4K12la-HDAC1 epigenetic axis governs microglial state transitions during experimental autoimmune encephalomyelitis in female mice.Nature communications · 2026Article
- Metabolic reprogramming of myeloid cells in cancer: from lactate-NAMPT axis to AI-guided therapeutics.Experimental & molecular medicine · 2026Review
- Review
- Lactate acts as a metabolic brake on inflammation by repressing NLRP3 transcription via NF-κB inhibition.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Metabolic Perspective on Atherosclerosis: Macrophage Reprogramming and Novel Therapeutic Targets.Journal of the American Heart Association · 2026Review
- Integrative Transcriptomic Signature of tRNA-Derived Fragment Targets and Lactylation-Related Genes for Prostate Cancer Diagnosis.Cancer medicine · 2026Article
- Steroid hormone ouabain cooperates with NaActa pharmaceutica Sinica. B · 2026Article
- Trained immunity modulators: A new frontier in immunoregulation and disease intervention.Journal of advanced research · 2026Review
3 more citing papers are in PubMed but not listed here.
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Authors and funding
24 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trained immunity refers to the long-term memory of the innate immune cells. However, little is known about how environmental nutrient availability influences trained immunity. This study finds that physiologic carbon sources impact glucose contribution to the tricarboxylic acid (TCA) cycle and enhance cytokine production of trained monocytes. Our experiments demonstrate that trained monocytes preferentially employe lactate over glucose as a TCA cycle substrate, and lactate metabolism is required for trained immune cell responses to bacterial and fungal infection. Except for the contribution to the TCA cycle, endogenous lactate or exogenous lactate also supports trained immunity by regulating histone lactylation. Further transcriptome analysis, ATAC-seq, and CUT&Tag-seq demonstrate that lactate enhance chromatin accessibility in a manner dependent histone lactylation. Inhibiting lactate-dependent metabolism by silencing lactate dehydrogenase A (LDHA) impairs both lactate fueled the TCA cycle and histone lactylation. These findings suggest that lactate is the hub of immunometabolic and epigenetic programs in trained immunity.
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