{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:15:32Z","timestamp":1791645332477,"version":"4.3.4"},"reference-count":42,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"9","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:p>Gain-of-function mutations in NLRP3 are linked to cryopyrin-associated periodic syndromes (CAPS). Although NLRP3 autoinflammasome assembly triggers inflammatory cytokine release, its activation mechanisms are not fully understood. Our study used a functional genetic approach to identify regulators of NLRP3 inflammasome formation. We identified the HSP90\u03b2-SGT1 chaperone complex as crucial for autoinflammasome activation in CAPS. A deficiency in HSP90\u03b2, but not in HSP90\u03b1, impaired the formation of ASC specks without affecting the priming and expression of inflammasome components. Conversely, activating NLRP3 with stimuli such as nigericin or alum bypassed the need for SGT1 and HSP90\u03b2, suggesting the existence of alternative inflammasome assembly pathways. The role of HSP90\u03b2 was further demonstrated in PBMCs derived from CAPS patients. In these samples, the pathological constitutive secretion of IL-1\u03b2 could be suppressed using a pharmacological inhibitor of HSP90\u03b2. This finding underscores the potential of SGT1-HSP90\u03b2 modulation as a therapeutic strategy in CAPS while preserving NLRP3\u2019s physiological functions.<\/jats:p>","DOI":"10.1126\/sciadv.adj6289","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T18:59:54Z","timestamp":1709146794000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":16,"title":["HSP90\u03b2 controls NLRP3 autoactivation"],"prefix":"10.1126","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4379-3050","authenticated-orcid":true,"given":"Lotte","family":"Spel","sequence":"first","affiliation":[{"name":"Department of Immunobiology, University of Lausanne, 155 Ch. des Boveresses, Epalinges 1066, 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