Evidence map›Paper›PMID 25729923›Full record

ArticleNature immunology2015

IL-37 requires the receptors IL-18Rα and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction.

Claudia A Nold-Petry, Camden Y Lo, Ina Rudloff, Kirstin D Elgass, Suzhao Li, Michael P Gantier, Amelie S Lotz-Havla, Søren W Gersting, Steven X Cho, Jason C Lao and 11 more

Abstract read
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In one paragraph

Article in Nature immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 243 papers.

0numbers the graph read from it
0cells of the map it votes in
243citing papers in PubMed
18.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

243 citing papers in PubMed, 434 citations in OpenAlex.

  1. Gut microbes · 2026
    Article
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  6. Atopic Dermatitis: New Targets and Emerging Systemic Therapies.American journal of clinical dermatology · 2026
    Review
  7. Review
  8. Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. IL-1 family cytokines in inflammation and immunity.Cellular & molecular immunology · 2025
    Review

183 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

21 authors at 10 institutions in 5 countries.

Claudia A Nold-Petry1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia.
Camden Y Lo1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Monash Micro Imaging, Monash University, Melbourne, Australia.
Ina Rudloff1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia.
Kirstin D ElgassMonash Micro Imaging, Monash University, Melbourne, Australia.
Suzhao LiDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Michael P Gantier1] Centre for Cancer Research, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Molecular and Translational Science, Monash University, Melbourne, Australia.ORCID 000000033740698X
Amelie S Lotz-HavlaMolecular Pediatrics, Ludwig-Maximilians University, Munich, Germany.
Søren W GerstingMolecular Pediatrics, Ludwig-Maximilians University, Munich, Germany.
Steven X Cho1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia.
Jason C Lao1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia.
Andrew M Ellisdon1] Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia. [2] Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Australia.
Björn RotterGenXPro, Frankfurt, Germany.
Tania AzamDepartment of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Niamh E Mangan1] Department of Molecular and Translational Science, Monash University, Melbourne, Australia. [2] Centre for Innate Immunity and Infectious Diseases, MIMR-PHI Institute of Medical Research, Melbourne, Australia.
Fernando J RosselloVictorian Bioinformatics Consortium, Monash University, Melbourne, Australia.ORCID 0000000338858777
James C Whisstock1] Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia. [2] Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Melbourne, Australia.
Philip BuflerDepartment of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians University, Munich, Germany.
Cecilia GarlandaHumanitas Clinical and Research Center, Rozzano, Italy.
Alberto Mantovani1] Humanitas Clinical and Research Center, Rozzano, Italy. [2] Humanitas University, Rozzano, Italy.
Charles A Dinarello1] Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA. [2] Radboud University Medical Centre, Nijmegen, the Netherlands.
Marcel F Nold1] Ritchie Centre, MIMR-PHI Institute of Medical Research, Melbourne, Victoria, Australia. [2] Department of Paediatrics, Monash University, Melbourne, Australia. [3] Department of Medicine, University of Colorado Denver, Aurora, Colorado, USA.
Hudson Institute of Medical Research · AUMonash University · AULudwig-Maximilians-Universität München · DEAustralian Research Council · AUHumanitas University · ITUniversity of Colorado Denver · USGenXPro (Germany) · DEMelbourne Bioinformatics · AUMonash Institute of Medical Research · AURadboud University Nijmegen · NL

Funding

University of Colorado Cancer Center Support Grant - Lung Cancer Patient-Derived Xenografts with Autologous Human Immune SystemsP30CA046934 · NCI · UNIVERSITY OF COLORADO DENVER · PI James V Degregori · 1988 to 2026
$117.0M
Yeast-based HTS Assay Technologies for ProteasesR01AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1985 to 2025
$8.5M
VitiligoR01AR045584 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI SPRITZ, RICHARD ANDREW · 1999 to 2014
$6.2M
Pathogenesis of Fever in ManR56AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 2016 to 2016
$311k
PATHOGENESIS OF FEVER IN HUMANSR37AI015614 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DINARELLO, CHARLES ANTHONY · 1988 to 1998
–
NCI NIH HHS CA-04 6934NIAID NIH HHS AI-15614NIAID NIH HHS R01 AI015614NIAMS NIH HHS AR-45584
6 · The paper itself

Abstract

Interleukin 37 (IL-37) and IL-1R8 (SIGIRR or TIR8) are anti-inflammatory orphan members of the IL-1 ligand family and IL-1 receptor family, respectively. Here we demonstrate formation and function of the endogenous ligand-receptor complex IL-37-IL-1R8-IL-18Rα. The tripartite complex assembled rapidly on the surface of peripheral blood mononuclear cells upon stimulation with lipopolysaccharide. Silencing of IL-1R8 or IL-18Rα impaired the anti-inflammatory activity of IL-37. Whereas mice with transgenic expression of IL-37 (IL-37tg mice) with intact IL-1R8 were protected from endotoxemia, IL-1R8-deficient IL-37tg mice were not. Proteomic and transcriptomic investigations revealed that IL-37 used IL-1R8 to harness the anti-inflammatory properties of the signaling molecules Mer, PTEN, STAT3 and p62(dok) and to inhibit the kinases Fyn and TAK1 and the transcription factor NF-κB, as well as mitogen-activated protein kinases. Furthermore, IL-37-IL-1R8 exerted a pseudo-starvational effect on the metabolic checkpoint kinase mTOR. IL-37 thus bound to IL-18Rα and exploited IL-1R8 to activate a multifaceted intracellular anti-inflammatory program.

Indexed as

AnimalsCell Linec-Mer Tyrosine KinaseGene Expression RegulationHumansImmunity, InnateInflammationInterleukin-1Interleukin-18 Receptor alpha SubunitLeukocytes, MononuclearLipopolysaccharidesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMiceMice, TransgenicNF-kappa Bc-Mer Tyrosine KinaseFYN protein, humanIL37 protein, humanInterleukin-1Interleukin-18 Receptor alpha SubunitLipopolysaccharidesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMERTK protein, humanMTOR protein, humanNF-kappa BP62 protein, humanProto-Oncogene ProteinsProto-Oncogene Proteins c-fynPTEN PhosphohydrolasePTEN protein, humanReceptor Protein-Tyrosine KinasesReceptors, Interleukin-1RNA-Binding ProteinsRNA, Small InterferingSIGIRR protein, humanSTAT3 protein, humanSTAT3 Transcription FactorTOR Serine-Threonine Kinases

Identifiers

PMID25729923
OpenAlexW2093194698

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Registered trials

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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.