{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:53:24Z","timestamp":1787014404583,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T00:00:00Z","timestamp":1769299200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Gout is associated with the upregulation of triggering receptor expressed on myeloid cells\u20101 (TREM\u20101) and soluble TREM\u20101 (sTREM\u20101). Cell activation signalling induced by monosodium urate (MSU) crystals and TREM\u20101 signalling both converge on spleen tyrosine kinase (Syk). The aim of this study was to decipher the role of the TREM\u20101 peptidomimetic inhibitor LP17, as well as Syk inhibitor, and their interaction during MSU\u2010induced cell inflammation, focusing on NLRP3 inflammasome activation, IL\u20101\u03b2 production and pyroptosis. In MSU\u2010activated cells, both LP17 and Syk inhibitor (iSyk) significantly reduced the secretion of IL\u20101\u03b2 and the release and activity of caspase\u20101. LP17 changed the phosphorylation of Syk, indicating that inhibition of TREM\u20101 modulates the activation state of Syk. Both LP17 and iSyk reduced the level of NLRP3\u2010induced apoptosis\u2010associated speck\u2010like protein (ASC) transcripts and MSU\u2010induced immunolabelling of ASC. Under confocal immunomicroscopy, TREM\u20101 in MSU\u2010crystal\u2010activated cells was localised to the same perimembranal compartment with NLRP3 inflammasome; inhibition of TREM\u20101 hindered the colocalisation of Syk with ASC. These results were corroborated by use of the in\u00a0vitro ASC oligomerszation assay that showed that blocking TREM\u20101 induced Syk redistribution from ASC complexes, indicating that LP17 can repress the ability of Syk to incorporate into the forming ASC speckle. Additionally, unlike iSyk, LP17 hampered MSU\u2010induced cleavage of gasdermin D, the hallmark of pyroptosis. Together, our findings suggest that blocking TREM\u20101 may prove beneficial as a novel strategy in the treatment of gout as well as other inflammasome\u2010mediated diseases.<\/jats:p>","DOI":"10.1111\/imm.70108","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T06:05:58Z","timestamp":1769407558000},"page":"249-260","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>TREM<\/scp>\n                    \u20101 Blockade Inhibits Inflammasome Activation and Pyroptosis: Novel Insights on the Role of\n                    <scp>TREM<\/scp>\n                    \u20101 and Syk in Monosodium Urate Crystal\u2010Induced Inflammation"],"prefix":"10.1111","volume":"178","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0630-8762","authenticated-orcid":false,"given":"Yair","family":"Molad","sequence":"first","affiliation":[{"name":"Laboratory for Research of Inflammation Felsenstein Medical Research Center, Gray's Faculty of Medical and Health Sciences, Tel Aviv University  Tel Aviv Israel"},{"name":"Institute of Rheumatology, Rabin Medical Center\u2014Beilinson Hospital  Petach Tikva Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Lagovsky","sequence":"additional","affiliation":[{"name":"Laboratory for Research of Inflammation Felsenstein Medical Research Center, Gray's Faculty of Medical and Health Sciences, Tel Aviv University  Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitaly","family":"Kliminski","sequence":"additional","affiliation":[{"name":"Laboratory for Research of Inflammation Felsenstein Medical Research Center, Gray's Faculty of Medical and Health Sciences, Tel Aviv University  Tel Aviv 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