ArticleThe Journal of clinical investigation2019
Nonimmune cell-derived ICOS ligand functions as a renoprotective αvβ3 integrin-selective antagonist.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- An inducible co-stimulator ligand (ICOSL)-based peptide therapy for proteinuric kidney diseases targeting αvβ3 integrin.Molecular biomedicine · 2026Article
- Potential Role of the Urokinase-Type Plasminogen Activator Receptor-Integrin β3 Axis in Podocyte Adhesion Instability and Loss.Kidney international reports · 2026Article
- uPAR/suPAR Signaling and Organ Crosstalk in Cardiovascular-Kidney-Metabolic Syndrome.Circulation research · 2026Review
- Dysregulated Protease Homeostasis Defines Primary FSGS.Kidney360 · 2026Article
- Inducible T-Cell Co-Stimulator (ICOS) and ICOS Ligand: Dealing With a Two-Faced Cancer Immunoregulatory System.Cancer medicine · 2026Review
- ICOSL: more than a trigger of ICOS function.Cell communication and signaling : CCS · 2025Review
- Role of Balanced Involvement of the ICOS/ICOSL/Osteopontin Network in Cutaneous Wound Healing.International journal of molecular sciences · 2024Article
- A simple protocol to establish a conditionally immortalized mouse podocyte cell line.Scientific reports · 2024Article
- Integrin αVβ3 antagonist-c(RGDyk) peptide attenuates the progression of ossification of the posterior longitudinal ligament by inhibiting osteogenesis and angiogenesis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Deep Flow Cytometry Unveils Distinct Immune Cell Subsets in Inducible T Cell Co-Stimulator Ligand (ICOSL)- and ICOS-Knockout Mice during Experimental Autoimmune Encephalomyelitis.International journal of molecular sciences · 2024Article
- A20 regulates lymphocyte adhesion in murine neuroinflammation by restricting endothelial ICOSL expression in the CNS.The Journal of clinical investigation · 2023Article
- TGFBI remodels adipose metabolism by regulating the Notch-1 signaling pathway.Experimental & molecular medicine · 2023Article
- Role of the co-stimulatory molecule inducible T-cell co-stimulator ligand (ICOSL) in the progression of experimental metabolic dysfunction-associated steatohepatitis.Frontiers in immunology · 2023Article
- Targeting immune checkpoints in anti-neutrophil cytoplasmic antibodies associated vasculitis: the potential therapeutic targets in the future.Frontiers in immunology · 2023Review
- The O-glycosylating enzyme GALNT2 acts as an oncogenic driver in non-small cell lung cancer.Cellular & molecular biology letters · 2022Article
- ICOS-Fc as innovative immunomodulatory approach to counteract inflammation and organ injury in sepsis.Frontiers in immunology · 2022Article
- Role of endocytosis and trans-endocytosis in ICOS costimulator-induced downmodulation of the ICOS Ligand.Journal of leukocyte biology · 2021Article
- Inducible T-Cell Costimulator Mediates Lymphocyte/Macrophage Interactions During Liver Repair.Frontiers in immunology · 2021Article
- Osteopontin binds ICOSL promoting tumor metastasis.Communications biology · 2020Article
- Structural characterization of the ICOS/ICOS-L immune complex reveals high molecular mimicry by therapeutic antibodies.Nature communications · 2020Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Soluble urokinase receptor (suPAR) is a circulatory molecule that activates αvβ3 integrin on podocytes, causes foot process effacement, and contributes to proteinuric kidney disease. While active integrin can be targeted by antibodies and small molecules, endogenous inhibitors haven't been discovered yet. Here we report what we believe is a novel renoprotective role for the inducible costimulator ligand (ICOSL) in early kidney disease through its selective binding to podocyte αvβ3 integrin. Contrary to ICOSL's immune-regulatory role, ICOSL in nonhematopoietic cells limited the activation of αvβ3 integrin. Specifically, ICOSL contains the arginine-glycine-aspartate (RGD) motif, which allowed for a high-affinity and selective binding to αvβ3 and modulation of podocyte adhesion. This binding was largely inhibited either by a synthetic RGD peptide or by a disrupted RGD sequence in ICOSL. ICOSL binding favored the active αvβ3 rather than the inactive form and showed little affinity for other integrins. Consistent with the rapid induction of podocyte ICOSL by inflammatory stimuli, glomerular ICOSL expression was increased in biopsies of early-stage human proteinuric kidney diseases. Icosl deficiency in mice resulted in an increased susceptibility to proteinuria that was rescued by recombinant ICOSL. Our work identified a potentially novel role for ICOSL, which serves as an endogenous αvβ3-selective antagonist to maintain glomerular filtration.
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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.