ArticleNature communications2022
CXCL4 synergizes with TLR8 for TBK1-IRF5 activation, epigenomic remodeling and inflammatory response in human monocytes.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
27 citing papers in PubMed, 42 citations in OpenAlex.
- The role of IRF5 as an immune regulator.Biochemical Society transactions · 2026Review
- A cryptic symmetry switch allosterically controls how the PF4 self-protein turns into a pathogenic antigen.Nature communications · 2026Article
- Aging-Related Muscle Bmal1 Decline Contributes to Bone Loss in Mice via Enhancing IL-1α-Mediated Osteoclastogenesis.Aging cell · 2026Article
- Decoding Undesirable Inflammatory Responses of Nucleic Acid-Delivering Lipid Nanoparticles.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- CD14+CD16- monocytes exhibit NF-κB hyperactivation in biliary atresia: Clinical association and murine therapeutic validation.Hepatology communications · 2026Article
- STAMBP drives colorectal cancer progression via CXCR4 deubiquitination and bone marrow-derived suppressor cell recruitment.Genes and immunity · 2026Article
- CXCL4 and CXCL4L1 activate human macrophage via TLR4 signaling to modulate inflammatory responses.Cell insight · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Escape From X Chromosome Inactivation as a Driver of Plasmacytoid DC Heterogeneity in Health and Disease.Immunological reviews · 2025Review
- Beyond Antagonism: IL-4 Exploits TNF signaling to Shape Its Gene Expression Signature in Monocytes and Macrophages.bioRxiv : the preprint server for biology · 2025Article
- IL-10 targets IRF transcription factors to suppress IFN and inflammatory response genes by epigenetic mechanisms.Nature immunology · 2025Article
- Platelet activation stimulates macrophages to enhance ulcerative colitis through PF4/CXCR3 signaling.International journal of molecular medicine · 2025Article
- Fibroblast PI3K/AKT signaling and extracellular matrix homeostasis: mechanisms, targets, and delivery challenges.Frontiers in cell and developmental biology · 2025Review
- Review
- TBK1 and Caspase-8 suppress necroptosis but activate NLRP3 inflammasome activation during CXCL4 and TLR8 costimulation.Cell death discovery · 2024Article
- The path ahead for understanding Toll-like receptor-driven systemic autoimmunity.Current opinion in immunology · 2024Review
- Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- The multiple roles of interferon regulatory factor family in health and disease.Signal transduction and targeted therapy · 2024Review
- Emerging roles of TBK1 in cancer immunobiology.Trends in cancer · 2024Review
- Interferons and epigenetic mechanisms in training, priming and tolerance of monocytes and hematopoietic progenitors.Immunological reviews · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Regulation of endosomal Toll-like receptor (TLR) responses by the chemokine CXCL4 is implicated in inflammatory and fibrotic diseases, with CXCL4 proposed to potentiate TLR responses by binding to nucleic acid TLR ligands and facilitating their endosomal delivery. Here we report that in human monocytes/macrophages, CXCL4 initiates signaling cascades and downstream epigenomic reprogramming that change the profile of the TLR8 response by selectively amplifying inflammatory gene transcription and interleukin (IL)-1β production, while partially attenuating the interferon response. Mechanistically, costimulation by CXCL4 and TLR8 synergistically activates TBK1 and IKKε, repurposes these kinases towards an inflammatory response via coupling with IRF5, and activates the NLRP3 inflammasome. CXCL4 signaling, in a cooperative and synergistic manner with TLR8, induces chromatin remodeling and activates de novo enhancers associated with inflammatory genes. Our findings thus identify new regulatory mechanisms of TLR responses relevant for cytokine storm, and suggest targeting the TBK1-IKKε-IRF5 axis may be beneficial in inflammatory diseases.
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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.