ArticleProceedings of the National Academy of Sciences of the United States of America2012
Reverse signaling through the costimulatory ligand CD137L in epithelial cells is essential for natural killer cell-mediated acute tissue inflammation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 75 citations in OpenAlex.
- Natural killer cells in kidney immune surveillance, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- Single-cell analysis reveals an important role of CD137L+ macrophages in the host response to uropathogenic Escherichia coli infection in the bladder.PLoS pathogens · 2025Article
- CD137L promotes immune surveillance in melanoma via HLTF regulation.Nature communications · 2025Article
- Innate immune cells in acute and chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Group 1 innate lymphoid cells protect liver transplants from ischemia-reperfusion injury via an interferon gamma-mediated pathway.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Article
- Protective and pathogenic functions of innate lymphoid cells in transplantation.Clinical and experimental immunology · 2023Review
- Natural Killer Cells, as the Rising Point in Tissues, Are Forgotten in the Kidney.Biomolecules · 2023Review
- CD137 signaling aggravates myocardial ischemia-reperfusion injury by inhibiting mitophagy mediated NLRP3 inflammasome activation.Journal of geriatric cardiology : JGC · 2023Article
- Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking.EMBO molecular medicine · 2023Article
- Molecular Mechanisms of Rhabdomyolysis-Induced Kidney Injury: From Bench to Bedside.Kidney international reports · 2023Review
- Tissue-Dependent Adaptations and Functions of Innate Lymphoid Cells.Frontiers in immunology · 2022Review
- CD137L-macrophage induce lymphatic endothelial cells autophagy to promote lymphangiogenesis in renal fibrosis.International journal of biological sciences · 2022Article
- CD137 Signaling Is Critical in Fungal Clearance during SystemicJournal of fungi (Basel, Switzerland) · 2021Article
- Nrf2 Promotes Inflammation in Early Myocardial Ischemia-ReperfusionFrontiers in immunology · 2021Article
- CCR5-mediated Recruitment of NK Cells to the Kidney Is a Critical Step for Host Defense to SystemicImmune network · 2020Article
- Recent Advances in the Role of Natural Killer Cells in Acute Kidney Injury.Frontiers in immunology · 2020Review
- CD137L-DCs, Potent Immune-Stimulators-History, Characteristics, and Perspectives.Frontiers in immunology · 2019Review
- Natural Killer Cells in Kidney Health and Disease.Frontiers in immunology · 2019Review
- The Costimulatory Pathways and T Regulatory Cells in Ischemia-Reperfusion Injury: A Strong Arm in the Inflammatory Response?International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Renal ischemia-reperfusion injury (IRI) after kidney transplantation is a major cause of delayed graft function. Even though IRI is recognized as a highly coordinated and specific process, the pathways and mechanisms through which the innate response is activated are poorly understood. In this study, we used a mouse model of acute kidney IRI to examine whether the interactions of costimulatory receptor CD137 and its ligand (CD137L) are involved in the early phase of acute kidney inflammation caused by IRI. We report here that the specific expressions of CD137 on natural killer cells and of CD137L on tubular epithelial cells (TECs) are required for acute kidney IRI. Reverse signaling through CD137L in TECs results in their production of the chemokine (C-X-C motif) receptor 2 ligands CXCL1 and CXCL2 and the subsequent induction of neutrophil recruitment, resulting in a cascade of proinflammatory events during kidney IRI. Our findings identify an innate pathogenic pathway for renal IRI involving the natural killer cell-TEC-neutrophil axis, whereby CD137-CD137L interactions provide the causal contribution of epithelial cell dysregulation to renal IRI. The CD137L reverse signaling pathway in epithelial cells therefore may represent a good target for blocking the initial stage of inflammatory diseases, including renal IRI.
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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.