Projects per year
Abstract
Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor of inflammation and immunity. We determined the crystal structure of IL-37 to establish the anti-inflammatory mechanism of this key cytokine in view of developing IL-37-based therapies. We found that two β-trefoil fold IL-37 molecules form a head-to-head dimer that is stable in solution. IL-37 variants mutated to convert the cytokine into an obligate monomer were up to 13-fold more effective than the dimer in suppressing proinflammatory events both in primary human blood cells and in vivo in murine endotoxic shock. Therapeutic exploitation of the powerful anti-inflammatory properties of monomeric IL-37 may prove beneficial in treating a wide range of inflammatory and autoimmune disorders.
Original language | English |
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Article number | eaaj1548 |
Number of pages | 12 |
Journal | Science Immunology |
Volume | 2 |
Issue number | 8 |
DOIs | |
Publication status | Published - 10 Feb 2017 |
Projects
- 3 Finished
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ARC Centre of Excellence in Advanced Molecular Imaging
Whisstock, J. (Primary Chief Investigator (PCI)), Abbey, B. (Chief Investigator (CI)), Nugent, K. A. (Chief Investigator (CI)), Quiney, H. M. (Chief Investigator (CI)), Godfrey, D. I. (Chief Investigator (CI)), Heath, W. (Chief Investigator (CI)), Fairlie, D. P. (Chief Investigator (CI)), Chapman, H. (Partner Investigator (PI)), Peele, A. (Partner Investigator (PI)), Davey, J. (Partner Investigator (PI)) & Wittmann, A. (Project Manager)
30/06/14 → 31/03/21
Project: Research
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Taking the First Steps from Promise to Product: Exploration of the Newly Discovered Interleukin 37 Receptor Complex and Its Signaling Pathways
Nold, M. (Primary Chief Investigator (PCI)), Nold, C. (Chief Investigator (CI)) & Rosado, C. (Chief Investigator (CI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/13 → 31/12/15
Project: Research
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Unraveling IL-1F7: A neglected IL-1 family member with big-stage potential
Nold, M. (Primary Chief Investigator (PCI)) & Nold, C. (Chief Investigator (CI))
NHMRC - National Health and Medical Research Council (Australia)
1/01/11 → 31/12/13
Project: Research
Equipment
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Australian Synchrotron
Office of the Vice-Provost (Research and Research Infrastructure)Facility/equipment: Facility