Extracellular forms of IL-37 inhibit innate inflammation in vitro and in vivo but require the IL-1 family decoy receptor IL-1R8
Abstract
Interleukin-1 family members are highly inflammatory but IL-37 member broadly suppresses inflammation and specific immunity. Initially, the mechanism of this suppression was shown to be via translocation to the nucleus following cleavage of the precursor by intracellular caspase-1. We now show that recombinant forms of IL-37 limit inflammation by extracellular binding to surface receptors but require the IL-1 family decoy receptor IL-1R8. Unexpectedly, picomolar concentrations of the IL-37 precursor optimally suppress IL-1β, IL-6, and TNFα production from human blood M1 macrophages, suggesting a unique function for a coreceptor function of IL-1R8. Assessment of IL-37 as well as IL-1R8 levels may provide previously unidentified insights into how the host limits inflammation.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- February 2015
- DOI:
- 10.1073/pnas.1424626112
- Bibcode:
- 2015PNAS..112.2497L