ArticleProceedings of the National Academy of Sciences of the United States of America2019
Interleukin-37 monomer is the active form for reducing innate immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
- IL-37/IL-1R8 axis: a novel major mechanism of control at the interface between tumor and immune cells.Oncoimmunology · 2026Review
- Research progress on the role of IL‑37 in gynecological and obstetrics‑related diseases (Review).International journal of molecular medicine · 2026Review
- Interleukin-37 does not confer protection against stone formation or kidney injury at the peak of disease in a murine calcium oxalate model.Urolithiasis · 2026Article
- Cytokine multimerization: when more is more and sometimes less.Nature reviews. Immunology · 2026Review
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- IL-18 Binding Protein, a biomarker of strength maintenance after surgery but reduced physical performance in age-related sarcopenia.PloS one · 2026Article
- High-dose IL-37 promotes inflammatory activity of macrophage via Preferential ligation of the IL-18Rα.Scientific reports · 2025Article
- Interleukin-37 in respiratory diseases: molecular mechanisms and immune modulation.Frontiers in immunology · 2025Review
- Recombinant expression, downstream optimization, and therapeutic evaluation of recombinant human interleukin-37 for cancer therapy.Biotechnology letters · 2024Article
- Rational design of monomeric IL37 variants guided by stability and dynamical analyses of IL37 dimers.Computational and structural biotechnology journal · 2024Article
- IL-37d suppresses Rheb-mTORC1 axis independently of TCS2 to alleviate alcoholic liver disease.Communications biology · 2024Article
- Thirteen years to get from b to a: one of the neglected isoforms of IL-37 enters the stage.Cellular & molecular immunology · 2024Article
- The nuclear cytokine IL-37a controls lethal cytokine storms primarily via IL-1R8-independent transcriptional upregulation of PPARγ.Cellular & molecular immunology · 2023Article
- A novel approach to achieving more efficient production of the mature form of human IL-37 in plants.Transgenic research · 2023Article
- Novel insights into IL-37: an anti-inflammatory cytokine with emerging roles in anti-cancer process.Frontiers in immunology · 2023Review
- Plant-produced recombinant cytokines IL-37b and IL-38 modulate inflammatory response from stimulated human PBMCs.Scientific reports · 2022Article
- Article
- Human and Bacterial Toll-Interleukin Receptor Domains Exhibit Distinct Dynamic Features and Functions.Molecules (Basel, Switzerland) · 2022Article
- Review
- Marine-Derived Piericidin Diglycoside S18 Alleviates Inflammatory Responses in the Aortic Valve via Interaction with Interleukin 37.Oxidative medicine and cellular longevity · 2022Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Interleukin-37 (IL-37), a member of the IL-1 family of cytokines, is a fundamental suppressor of innate and acquired immunities. Here, we used an integrative approach that combines biophysical, biochemical, and biological studies to elucidate the unique characteristics of IL-37. Our studies reveal that single amino acid mutations at the IL-37 dimer interface that result in the stable formation of IL-37 monomers also remain monomeric at high micromolar concentrations and that these monomeric IL-37 forms comprise higher antiinflammatory activities than native IL-37 on multiple cell types. We find that, because native IL-37 forms dimers with nanomolar affinity, higher IL-37 only weakly suppresses downstream markers of inflammation whereas lower concentrations are more effective. We further show that IL-37 is a heparin binding protein that modulates this self-association and that the IL-37 dimers must block the activity of the IL-37 monomer. Specifically, native IL-37 at 2.5 nM reduces lipopolysaccharide (LPS)-induced vascular cell adhesion molecule (VCAM) protein levels by ∼50%, whereas the monomeric D73K mutant reduced VCAM by 90% at the same concentration. Compared with other members of the IL-1 family, both the N and the C termini of IL-37 are extended, and we show they are disordered in the context of the free protein. Furthermore, the presence of, at least, one of these extended termini is required for IL-37 suppressive activity. Based on these structural and biological studies, we present a model of IL-37 interactions that accounts for its mechanism in suppressing innate inflammation.
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