ArticleNature immunology2018
PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing.
Article in Nature immunology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 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
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Who cites it
95 citing papers in PubMed, 145 citations in OpenAlex.
- Integrative Single-Cell Transcriptomics, Multi-Omics Analyses, and Computational Pharmacology Reveal Macrophage Heterogeneity and the Putative THBS1-CD36 Axis in Coronary Atherosclerosis.Chemical biology & drug design · 2026Article
- TLR7 in systemic lupus erythematosus: genetics and emerging therapies.Nature reviews. Rheumatology · 2026Review
- Chikungunya virus persists in joint-associated macrophages and promotes chronic disease in mice.Nature microbiology · 2026Article
- Physiological and Metabolic Effects ofAnimals : an open access journal from MDPI · 2026Article
- Cell-Free DNA-Based Theranostics for Inflammatory Disorders.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Spatially resolved transcriptome-metabolome integration reveals region-specific glial lipid dysregulation associated with Alzheimer's pathology.bioRxiv : the preprint server for biology · 2026Article
- Multiomics identifies a cholesterol-TFEB-PLD3-TLR9 axis driving immunosuppressive tumor-associated macrophage polarization in esophageal squamous cell carcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Identification of potential predictive biomarkers during JAK-inhibitor therapies in rheumatoid arthritis.Human genomics · 2025Article
- Phospholipase D: emerging therapeutic targets in signaling, metabolism, and immune-oncology.Cell communication and signaling : CCS · 2025Review
- Mechanistic insights into single-stranded DNA degradation by lysosomal exonucleases PLD3 and PLD4 from structural snapshots.Nature communications · 2025Article
- Macrophage Phospholipase D3 promotes atherosclerosis via exacerbating foam cell formation and inducing inflammatory responses.International journal of cardiology. Heart & vasculature · 2025Article
- The lysosomal catabolism of nucleic acids-critical regulators of the innate immune system.Nucleic acids research · 2025Review
- Multi-organ single-cell analysis reveals PLD4 as a biomarker and potential therapeutic target of blastic plasmacytoid dendritic cell neoplasm.Cancer cell international · 2025Article
- Article
- Exosome-Mediated Delivery of a PLD1 Modulator Overcomes Bioavailability Hurdles to Target Synaptopathy in Neurodegenerative Diseases.Pharmaceutical research · 2025Article
- Lysosomal RNA profiling reveals targeting of specific types of RNAs for degradation.bioRxiv : the preprint server for biology · 2025Article
- Proteomic aging signatures across mouse organs and life stages.The EMBO journal · 2025Article
- Innate immune responses to lysosomal nucleic acid stress.Journal of biochemistry · 2025Review
- Luminal Phospholipase D Attacks Bacterial Membranes in Dictyostelium discoideum Phagosomes.Molecular microbiology · 2025Article
- Postnatal Epigenetic Alterations in Calves Persistently Infected with Bovine Viral Diarrhea Virus.Viruses · 2025Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 3 countries.
Funding
Abstract
The sensing of microbial genetic material by leukocytes often elicits beneficial pro-inflammatory cytokines, but dysregulated responses can cause severe pathogenesis. Genome-wide association studies have linked the gene encoding phospholipase D3 (PLD3) to Alzheimer's disease and have linked PLD4 to rheumatoid arthritis and systemic sclerosis. PLD3 and PLD4 are endolysosomal proteins whose functions are obscure. Here, PLD4-deficient mice were found to have an inflammatory disease, marked by elevated levels of interferon-γ (IFN-γ) and splenomegaly. These phenotypes were traced to altered responsiveness of PLD4-deficient dendritic cells to ligands of the single-stranded DNA sensor TLR9. Macrophages from PLD3-deficient mice also had exaggerated TLR9 responses. Although PLD4 and PLD3 were presumed to be phospholipases, we found that they are 5' exonucleases, probably identical to spleen phosphodiesterase, that break down TLR9 ligands. Mice deficient in both PLD3 and PLD4 developed lethal liver inflammation in early life, which indicates that both enzymes are needed to regulate inflammatory cytokine responses via the degradation of nucleic acids.
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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.