We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Myeloid cell–derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement.
- Authors
Sullivan, Graeme P.; Davidovich, Pavel; Muñoz-Wolf, Natalia; Ward, Ross W.; Hernandez Santana, Yasmina E.; Clancy, Danielle M.; Gorman, Aoife; Najda, Zaneta; Turk, Boris; Walsh, Patrick T.; Lavelle, Ed C.; Martin, Seamus J.
- Abstract
Interleukin-1 (IL-1) family cytokines are key barrier cytokines that are typically expressed as inactive, or partially active, precursors that require proteolysis within their amino termini for activation. IL-37 is an enigmatic member of the IL-1 family that has been proposed to be activated by caspase-1 and to exert anti-inflammatory activity through engagement of the IL-18R and SIGIRR. However, here we show that the longest IL-37 isoform, IL-37b, exhibits robust proinflammatory activity upon amino-terminal proteolysis by neutrophil elastase or cathepsin S. In sharp contrast, caspase-1 failed to process or activate IL-37 at concentrations that robustly activated its canonical substrate, IL-1β. IL-37 and IL-36 exhibit high structural homology, and, consistent with this, a K53-truncated form of IL-37, mimicking the cathepsin S–processed form of this cytokine,was found to exert its proinflammatory effects via IL-36 receptor engagement and produced an inflammatory signature practically identical to IL-36. Administration of K53-truncated IL-37b intraperitoneally into wild-type mice also elicited an inflammatory response that was attenuated in IL-36R−/− animals. These data demonstrate that, in common with other IL-1 family members, mature IL-37 can also elicit proinflammatory effects upon processing by specific proteases.
- Publication
Science Immunology, 2022, Vol 7, Issue 78, p1
- ISSN
2470-9468
- Publication type
Article
- DOI
10.1126/sciimmunol.ade5728