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- Title
Homodimerization attenuates the anti-inflammatory activity of interleukin-37.
- Authors
Ellisdon, Andrew M.; Nold-Petry, Claudia A.; D’Andrea, Laura; Cho, Steven X.; Lao, Jason C.; Rudloff, Ina; Ngo, Devi; Lo, Camden Y.; Soares da Costa, Tatiana P.; Perugini, Matthew A.; Conroy, Paul J.; Whisstock, James C.; Nold, Marcel F.
- 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.
- Publication
Science Immunology, 2017, Vol 2, Issue 8, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.aaj1548