Homodimerization attenuates the anti-inflammatory activity of interleukin-37

Andrew M. Ellisdon, Claudia A. Nold-Petry, Laura D'Andrea, Steven X. Cho, Jason C. Lao, Ina Rudloff, Devi Ngo, Camden Y. Lo, Tatiana P Soares da Costa, Matthew A. Perugini, Paul J. Conroy, James C. Whisstock, Marcel F. Nold

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32 Citations (Scopus)


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 languageEnglish
Article numbereaaj1548
Number of pages12
JournalScience Immunology
Issue number8
Publication statusPublished - 10 Feb 2017

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