ArticleThe Journal of biological chemistry2022
Structural basis of human IL-18 sequestration by the decoy receptor IL-18 binding protein in inflammation and tumor immunity.
Article in The Journal of biological chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 26 citations in OpenAlex.
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- The Roles of Interleukin-18 in Inflammation and Autoimmune Disease.Clinical reviews in allergy & immunology · 2026Review
- Association of elevated serum active IL-18 levels with cytokine profiles and clinical features in adult-onset still's disease.Frontiers in immunology · 2026Article
- Engineered IL-18 variants with half-life extension and improved stability for cancer immunotherapy.Journal for immunotherapy of cancer · 2025Article
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- Development of anti-murine IL-18 binding protein antibodies to stimulate IL-18 bioactivity.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- The NLRP3-P2X7 Axis and Cytokine Crosstalk in Alzheimer's Disease: Mechanisms, Implications, and Therapeutic Opportunities.CNS & neurological disorders drug targets · 2025Review
- Article
- Interleukin‑18 binding protein: Biological properties and roles in human and animal immune regulation (Review).Biomedical reports · 2024Review
- [Clinical significance of IL-18 and IL-18-binding protein in bone marrow of patients with myelodysplastic syndrome].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- Article
- Molecular cloning, characterization and gene expression analysis of twelve interleukins in obscure pufferFish and shellfish immunology reports · 2023Article
- Article
- SIRT1 regulates hepatocyte programmed cell death via GSDME - IL18 axis in human and mouse liver transplantation.Cell death & disease · 2023Article
- mRNAs encoding IL-12 and a decoy-resistant variant of IL-18 synergize to engineer T cells for efficacious intratumoral adoptive immunotherapy.Cell reports. Medicine · 2023Article
- Review
- A small non-interface surface epitope in human IL18 mediates the dynamics and self-assembly of IL18-IL18BP heterodimers.Computational and structural biotechnology journal · 2023Article
- Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases.Biomedicines · 2022Review
- Interleukin-18 cytokine in immunity, inflammation, and autoimmunity: Biological role in induction, regulation, and treatment.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human Interleukin-18 (IL-18) is an omnipresent proinflammatory cytokine of the IL-1 family with central roles in autoimmune and inflammatory diseases and serves as a staple biomarker in the evaluation of inflammation in physiology and disease, including the inflammatory phase of COVID-19. The sequestration of IL-18 by its soluble decoy receptor IL-18-Binding Protein (IL-18BP) is critical to the regulation of IL-18 activity. Since an imbalance in expression and circulating levels of IL-18 is associated with disease, structural insights into how IL-18BP outcompetes binding of IL-18 by its cognate cell-surface receptors are highly desirable; however, the structure of human IL-18BP in complex with IL-18 has been elusive. Here, we elucidate the sequestration mechanism of human IL-18 mediated by IL-18BP based on the crystal structure of the IL-18:IL-18BP complex. These detailed structural snapshots reveal the interaction landscape leading to the ultra-high affinity of IL-18BP toward IL-18 and identify substantial differences with respect to previously characterized complexes of IL-18 with IL-18BP of viral origin. Furthermore, our structure captured a fortuitous higher-order assembly between IL-18 and IL-18BP coordinated by a disulfide-bond distal to the binding surface connecting IL-18 and IL-18BP molecules from different complexes, resulting in a novel tetramer with 2:2 stoichiometry. This tetrapartite assembly was found to restrain IL-18 activity more effectively than the canonical 1:1 complex. Collectively, our findings provide a framework for innovative, structure-driven therapeutic strategies and further functional interrogation of IL-18 in physiology and disease.
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