ArticleProceedings of the National Academy of Sciences of the United States of America2020
TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 280 papers.
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Who cites it
280 citing papers in PubMed, 431 citations in OpenAlex.
- Apoptotic body-encapsulated nanoparticles regulate inflammation through macrophage polarization mediated by lactic acid.Annals of medicine · 2026Article
- Lactylation in influenza a virus infection: Current evidence, knowledge gaps, and future perspectives.Virulence · 2026Review
- Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism.Annals of medicine · 2026Review
- H4K12 Lactylation Impairs Dopaminergic Neuron Energy Metabolism via the HIF-1α/NDUFS1 Pathway in Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ACAT1-Mediated SP1-K694 Lactylation Promotes M1 Macrophage Polarization via TREM1 Transcription in COPD.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Deficiency of protein kinase Cδ reprograms macrophage immunometabolism to suppress pyroptosis and stabilize atherosclerotic plaques.Experimental & molecular medicine · 2026Article
- Lactate-dependent regulation of ferroptosis: redox homeostasis, lactylation, and translational perspectives.Apoptosis : an international journal on programmed cell death · 2026Review
- Lactylation Modification and Esophageal Cancer: Research Progress From Hypoxia-Induced Metabolic Reprogramming to Immune Escape.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- An externally validated lactylation-associated prognostic signature for overall survival prediction in lung adenocarcinoma identifiesTranslational cancer research · 2026Article
- Protein lactylation in health and diseases: molecular mechanisms, biological significance, and clinical implications.Signal transduction and targeted therapy · 2026Review
- Lactylation-driven therapeutic resistance in cancer: Mechanisms and therapeutic opportunities.Genes & diseases · 2026Review
- Training PBertKla on an Integrated Multi-Source Dataset with a Machine-Learning Layer for Lysine Lactylation Site Prediction.International journal of molecular sciences · 2026Article
- A Novel Approach to Neuropathic Pain Treatment: Lactylation Targeting Microglia.Molecular neurobiology · 2026Review
- Lactylation: a promising target for musculoskeletal disorders via interactions with chronic inflammation.Journal of advanced research · 2026Review
- Mechanistic Insights Into Recurrent Implantation Failure: The Lactate-H3K18la-SLC7A11 Axis Explored via Endometrial Organoid and Blastoid-Endometrial Cell Implantation Models.Cell proliferation · 2026Article
- S100A9 lactylation facilitated sepsis-related acute respiratory distress syndrome via promoting transcription activation of IL-1β in macrophages.Cell communication and signaling : CCS · 2026Article
- Review
- Roles of efferocytosis in wound repair: Process, cells, and signals.Genes & diseases · 2026Review
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- Enhanced Bioactivity ofFood science & nutrition · 2026Article
220 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Macrophages respond to microbial ligands and various noxious cues by initiating an inflammatory response aimed at eliminating the original pathogenic insult. Transition of macrophages from a proinflammatory state to a reparative state, however, is vital for resolution of inflammation and return to homeostasis. The molecular players governing this transition remain poorly defined. Here, we find that the reparative macrophage transition is dictated by B-cell adapter for PI3K (BCAP). Mice harboring a macrophage-specific deletion of BCAP fail to recover from and succumb to dextran sulfate sodium-induced colitis due to prolonged intestinal inflammation and impaired tissue repair. Following microbial stimulation, gene expression in WT macrophages switches from an early inflammatory signature to a late reparative signature, a process that is hampered in BCAP-deficient macrophages. We find that absence of BCAP hinders inactivation of FOXO1 and GSK3β, which contributes to their enhanced inflammatory state. BCAP deficiency also results in defective aerobic glycolysis and reduced lactate production. This translates into reduced histone lactylation and decreased expression of reparative macrophage genes. Thus, our results reveal BCAP to be a critical cell-intrinsic switch that regulates transition of inflammatory macrophages to reparative macrophages by imprinting epigenetic changes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.