ArticleThe EMBO journal2024
Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis.
Article in The EMBO journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- A systematic review of protein post-translational modifications in sepsis.Molecular biology reports · 2025Pooled it
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Aspirin-Derived Salicyl-CoA Drives Histone Lysine Salicylation Regulated by CBP and SIRT2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Review
- [Anti-inflammatory Mechanisms of Human Resistin Through Activation of Peroxisome Proliferator-Activated Receptor γ].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026Article
- Article
- Epigenetics-mediated pathological alterations and their diagnostic and therapeutic potential in sepsis-associated acute kidney injury.Clinical epigenetics · 2026Review
- Immune regulation and therapeutic targets in sepsis: insights from single-cell transcriptomics.Frontiers in immunology · 2026Review
- Phenylacetylglutamine exacerbates sepsis-induced cardiac dysfunction and left ventricular remodeling via the ferroptosis and TLR4/NF-κB pathway.Frontiers in cardiovascular medicine · 2026Article
- Pattern recognition receptor signaling in otitis media: immune crosstalk and pathogenic mechanisms.Frontiers in immunology · 2026Review
- The Research Progress of Tumor-Associated Macrophages in Prostate Cancer.Journal of immunology research · 2026Review
- Curcumol overcomes cisplatin resistance and rewires glycolysis-H3K9la-ORC6 axis to trigger ferroptosis in bladder cancer.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2025Article
- Sodium butyrate inhibits colorectal cancer development by reducing M2 macrophage polarization and PD-L1 expression.mSystems · 2025Article
- Global Profiling of the Proteome and Acetylome in Mice with Abdominal Aortic Aneurysms.ACS omega · 2025Article
- Macrophages: sentinels, warriors, and healers.Human molecular genetics · 2025Review
- LPS mediates cuproptosis and inflammation in THP-1 macrophages through HKDC1.Acta biochimica et biophysica Sinica · 2025Article
- Trimming the fat: a brief review of lipids at the host-pathogen interface.Infection and immunity · 2025Review
- Therapeutic potential of elafibranor in alcohol-associated liver disease: Insights into macrophage modulation and fibrosis reduction.World journal of biological chemistry · 2025Review
- The molecular interplay among gut dysbiosis, adipose tissue, and metabolite-derived damage-associated molecular patterns in metainflammation and atherogenesis.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis.
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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.