ArticlePLoS pathogens2012
Asparagine endopeptidase controls anti-influenza virus immune responses through TLR7 activation.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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.
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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
41 citing papers in PubMed, 65 citations in OpenAlex.
- Legumain in Acute Coronary Syndromes: A Substudy of the PLATO (Platelet Inhibition and Patient Outcomes) Trial.Journal of the American Heart Association · 2020Trial
- Microglial TLR7 contributes to traumatic brain injury-induced neuroinflammation in mice.Acta pharmacologica Sinica · 2026Article
- Phosphorylation of YBX1 in the Kidneys is Altered in Legumain Knockout-Mice.Journal of proteome research · 2026Article
- Renal macrophage TLR7 signaling in lupus nephritis: from pathogenic mechanisms to therapeutic opportunities.Frontiers in immunology · 2026Review
- Recent insights into the role of innate immunity in lupus.Human molecular genetics · 2025Review
- Review
- Integrative analysis of TBI data reveals Lgmn as a key player in immune cell-mediated ferroptosis.BMC genomics · 2023Article
- Activation of TLR7-mediated autophagy increases epileptic susceptibility via reduced KIF5A-dependent GABAExperimental & molecular medicine · 2023Article
- The Mammalian Cysteine Protease Legumain in Health and Disease.International journal of molecular sciences · 2022Review
- The subversion of toll-like receptor signaling by bacterial and viral proteases during the development of infectious diseases.Molecular aspects of medicine · 2022Review
- The Asparaginyl Endopeptidase Legumain: An Emerging Therapeutic Target and Potential Biomarker for Alzheimer's Disease.International journal of molecular sciences · 2022Review
- Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.Nature communications · 2022Article
- The NCF1 variant p.R90H aggravates autoimmunity by facilitating the activation of plasmacytoid dendritic cells.The Journal of clinical investigation · 2022Article
- Lysosomes: multifunctional compartments ruled by a complex regulatory network.FEBS open bio · 2022Review
- Lysosomes and lysosome-related organelles in immune responses.FEBS open bio · 2022Review
- Loss of legumain induces premature senescence and mediates aging-related renal fibrosis.Aging cell · 2022Article
- The Mechanism of Asparagine Endopeptidase in the Progression of Malignant Tumors: A Review.Cells · 2021Review
- The role of cysteine peptidases in coronavirus cell entry and replication: The therapeutic potential of cathepsin inhibitors.PLoS pathogens · 2020Review
- Conditionally Controlling Human TLR2 Activity via Trans-Cyclooctene Caged Ligands.Bioconjugate chemistry · 2020Article
- Cell Surface Expression of Endosomal Toll-Like Receptors-A Necessity or a Superfluous Duplication?Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular Toll-like receptors (TLRs) expressed by dendritic cells recognize nucleic acids derived from pathogens and play an important role in the immune responses against the influenza virus (IAV), a single-stranded RNA sensed by different receptors including TLR7. However, the importance of TLR7 processing in the development of anti-viral immune responses is not known. Here we report that asparagine endopeptidase (AEP) deficient mice are unable to generate a strong anti-IAV response, as demonstrated by reduced inflammation, cross presentation of cell-associated antigens and priming of CD8(+) T cells following TLR7-dependent pulmonary infection induced by IAV. Moreover, AEP deficient lung epithelial- or myeloid-cells exhibit impaired TLR7 signaling due to defective processing of this receptor. Indeed, TLR7 requires a proteolytic cleavage by AEP to generate a C-terminal fragment competent for signaling. Thus, AEP activity is critical for TLR7 processing, opening new possibilities for the treatment of influenza and TLR7-dependent 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.