ArticleJournal of immunology (Baltimore, Md. : 1950)2015
CD13 restricts TLR4 endocytic signal transduction in inflammation.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 68 citations in OpenAlex.
- CD13 activation assembles phosphoinositide (PI) signaling complexes to regulate the actin cytoskeleton.Scientific reports · 2026Article
- INPP5D/SHIP1 is a dual regulator of endo-lysosome function and selective phagocytosis in human microglia.bioRxiv : the preprint server for biology · 2025Article
- Tropomodulin1 exacerbates inflammatory response in macrophages by negatively regulating LPS-induced TLR4 endocytosis.Cellular and molecular life sciences : CMLS · 2024Article
- The Implant-Induced Foreign Body Response Is Limited by CD13-Dependent Regulation of Ubiquitination of Fusogenic Proteins.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- The Role of the Ectopeptidase APN/CD13 in Cancer.Biomedicines · 2023Review
- Shifts in intestinal microbiota and improvement of sheep immune response to resist Salmonella infection using Toll-like receptor 4 (TLR4) overexpression.Frontiers in microbiology · 2023Article
- Macrophage-derived exosomal aminopeptidase N aggravates sepsis-induced acute lung injury by regulating necroptosis of lung epithelial cell.Communications biology · 2022Article
- CD13 orients the apical-basal polarity axis necessary for lumen formation.Nature communications · 2021Article
- Involvement of Toll-Like Receptor 4 in Decreased Vasopressor Response Following Trauma/Hemorrhagic Shock.Critical care explorations · 2021Article
- CD13 is a critical regulator of cell-cell fusion in osteoclastogenesis.Scientific reports · 2021Article
- Overexpression of Toll-like receptor 4 contributes to the internalization and elimination of Escherichia coli in sheep by enhancing caveolae-dependent endocytosis.Journal of animal science and biotechnology · 2021Article
- Primate innate immune responses to bacterial and viral pathogens reveals an evolutionary trade-off between strength and specificity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Coronavirus Receptors as Immune Modulators.Journal of immunology (Baltimore, Md. : 1950) · 2021Review
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Effect of BuShen JiangZhi Recipe on Atherosclerosis in ApoEEvidence-based complementary and alternative medicine : eCAM · 2021Article
- CD13: A Key Player in Multidrug Resistance in Cancer Chemotherapy.Oncology research · 2020Review
- Anticoagulant and signaling functions of antithrombin.Journal of thrombosis and haemostasis : JTH · 2020Review
- Antithrombin: An anticoagulant, anti-inflammatory and antibacterial serpin.Journal of thrombosis and haemostasis : JTH · 2020Article
- Therapeutic effect and mechanism of action of quercetin in a rat model of osteoarthritis.The Journal of international medical research · 2020Article
- When Innate Immunity Meets Angiogenesis-The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension.Frontiers in medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Dysregulation of the innate immune response underlies numerous pathological conditions. The TLR4 is the prototypical sensor of infection or injury that orchestrates the innate response via sequential activation of both cell surface and endocytic signaling pathways that trigger distinct downstream consequences. CD14 binds and delivers LPS to TLR4 and has been identified as a positive regulator of TLR4 signal transduction. It is logical that negative regulators of this process also exist to maintain the critical balance required for fighting infection, healing damaged tissue, and resolving inflammation. We showed that CD13 negatively modulates receptor-mediated Ag uptake in dendritic cells to control T cell activation in adaptive immunity. In this study, we report that myeloid CD13 governs internalization of TLR4 and subsequent innate signaling cascades, activating IRF-3 independently of CD14. CD13 is cointernalized with TLR4, CD14, and dynamin into Rab5(+) early endosomes upon LPS treatment. Importantly, in response to TLR4 ligands HMGB1 and LPS, p-IRF-3 activation and transcription of its target genes are enhanced in CD13(KO) dendritic cells, whereas TLR4 surface signaling remains unaffected, resulting in a skewed inflammatory response. This finding is physiologically relevant as ischemic injury in vivo provoked identical TLR4 responses. Finally, CD13(KO) mice showed significantly enhanced IFNβ-mediated signal transduction via JAK-STAT, escalating inducible NO synthase transcription levels and promoting accumulation of oxidative stress mediators and tissue injury. Mechanistically, inflammatory activation of macrophages upregulates CD13 expression and CD13 and TLR4 coimmunoprecipitate. Therefore, CD13 negatively regulates TLR4 signaling, thereby balancing the innate response by maintaining the inflammatory equilibrium critical to innate immune regulation.
Indexed as
Identifiers
What OpenQuestion holds
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.