ArticleProceedings of the National Academy of Sciences of the United States of America2016
Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 93 citations in OpenAlex.
- Immune response to DNA and RNA: structural insights, molecular mechanisms, and therapeutic targeting.Molecular biomedicine · 2026Review
- TLR7/9 and type I interferon signaling reprogram neutrophil NET responses and impair antibacterial defense in systemic lupus erythematosus.Cell press blue · 2026Article
- A Combined Transcriptomics and Proteomics Approach to Identify Immune Signatures in ANCA-Associated Glomerulonephritis.ACR open rheumatology · 2026Article
- Reduced late endosome/lysosome function promotes SLE through chronic PI3K activity and SHP-1/SHIP-1 defects.JCI insight · 2026Article
- Endosome traffic in rheumatic diseases: mechanistic insights and therapeutic opportunities.Nature reviews. Rheumatology · 2026Review
- Can Phagocytosis, Neutrophil Extracellular Traps, and IFN-α Production in Systemic Lupus Erythematosus Be Simultaneously Modulated? A Pharmacological Perspective.International journal of molecular sciences · 2026Review
- Tmem110 regulates the conformation of TRPML1 to maintain endolysosomal homeostasis and prevent mitochondrial DNA leakage and pathological self-DNA processing.Nature communications · 2026Article
- Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Article
- Apoptotic extracellular vesicles from peripancreatic adipose-derived mesenchymal stem cells ameliorate severe acute pancreatitis through the transcription factor EB-mediated autophagy-lysosomal pathway: an experimental study.International journal of surgery (London, England) · 2025Article
- A TLR7/9-IFNα-LDHB axis drives vital NET release and compromises antibacterial defense in lupus.bioRxiv : the preprint server for biology · 2025Article
- Live fast, die young: neutrophils streamline their metabolism to maximize inflammation.Infection and immunity · 2025Review
- Unraveling the role of lncRNAs and their associated nearby coding genes in the pathogenesis of systemic lupus erythematosus.Arthritis research & therapy · 2025Article
- The spectrum of lysosomal stress and damage responses: from mechanosensing to inflammation.EMBO reports · 2025Review
- Mechanisms and effects of activation of innate immunity by mitochondrial nucleic acids.International immunology · 2025Review
- Comprehensive Analysis of Ferroptosis Markers in Lupus Nephritis Based on Bioinformatics Analysis and Experimental Validation.Journal of inflammation research · 2025Article
- Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.Journal of lipid research · 2025Article
- Genetic and epigenetic regulation of inflammasomes: Role in atherosclerosis.Atherosclerosis · 2024Review
- Advances in non-viral mRNA delivery to the spleen.Biomaterials science · 2024Review
- Defective Lamtor5 Leads to Autoimmunity by Deregulating v-ATPase and Lysosomal Acidification.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Defects in clearing apoptotic debris disrupt tissue and immunological homeostasis, leading to autoimmune and inflammatory diseases. Herein, we report that macrophages from lupus-prone MRL/lpr mice have impaired lysosomal maturation, resulting in heightened ROS production and attenuated lysosomal acidification. Impaired lysosomal maturation diminishes the ability of lysosomes to degrade apoptotic debris contained within IgG-immune complexes (IgG-ICs) and promotes recycling and the accumulation of nuclear self-antigens at the membrane 72 h after internalization. Diminished degradation of IgG-ICs prolongs the intracellular residency of nucleic acids, leading to the activation of Toll-like receptors. It also promotes phagosomal membrane permeabilization, allowing dsDNA and IgG to leak into the cytosol and activate AIM2 and TRIM21. Collectively, these events promote the accumulation of nuclear antigens and activate innate sensors that drive IFNα production and heightened cell death. These data identify a previously unidentified defect in lysosomal maturation that provides a mechanism for the chronic activation of intracellular innate sensors in systemic lupus erythematosus.
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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.