dc.contributor.author | Walsh, Patrick | |
dc.contributor.author | Lavelle, Edward | |
dc.contributor.author | Munoz-Wolf, Natalia | |
dc.contributor.author | Martin, Seamus | |
dc.date.accessioned | 2024-05-30T11:18:05Z | |
dc.date.available | 2024-05-30T11:18:05Z | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022 | en |
dc.identifier.citation | Sullivan, G.P. and Davidovich, P. and Muñoz-Wolf, N. and Ward, R.W. and Hernandez Santana, Y.E. and Clancy, D.M. and Gorman, A. and Najda, Z. and Turk, B. and Walsh, P.T. and Lavelle, E.C. and Martin, S.J., Myeloid cell-derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement, Science immunology, 7, 78, 2022, eade5728 | en |
dc.identifier.other | Y | |
dc.description.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. | en |
dc.format.extent | eade5728 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Science immunology; | |
dc.relation.ispartofseries | 7; | |
dc.relation.ispartofseries | 78; | |
dc.rights | Y | en |
dc.title | Myeloid cell-derived proteases produce a proinflammatory form of IL-37 that signals via IL-36 receptor engagement | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/martinsj | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/walshp10 | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/lavellee | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/munozwon | |
dc.identifier.rssinternalid | 251095 | |
dc.identifier.doi | http://dx.doi.org/10.1126/sciimmunol.ade5728 | |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.identifier.orcid_id | 0000-0002-8539-3143 | |
dc.identifier.uri | http://hdl.handle.net/2262/108546 | |