{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T18:58:55Z","timestamp":1784919535139,"version":"3.55.0"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"45","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,11,11]]},"abstract":"<jats:p>\n            Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)\u2013primed\n            <jats:italic>Fadd<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <jats:italic>Ripk3<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            myeloid cells promoted interleukin-1\u03b2 (IL-1\u03b2) and IL-18 production through inflammasome activation. Caspase-8, caspase-1\/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated\n            <jats:italic>Fadd<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <jats:italic>Ripk3<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1\u03b2\/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic shock in\n            <jats:italic>Fadd<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            <jats:italic>Ripk3<\/jats:italic>\n            <jats:sup>\u2212\/\u2212<\/jats:sup>\n            mice, implying distinct death processes in other cell types. Cathepsin-B contributes to IETD-mediated inflammasome activation, as its inhibition or down-regulation limited IETD-elicited IL-1\u03b2 production. Therefore, the autophagy and cathepsin-B axis represents one of the pathways leading to atypical inflammasome activation when apoptosis and necroptosis are suppressed and capase-8 is inhibited in myeloid cells.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abn9912","type":"journal-article","created":{"date-parts":[[2022,11,11]],"date-time":"2022-11-11T18:58:20Z","timestamp":1668193100000},"source":"Crossref","is-referenced-by-count":32,"title":["Caspase-8 inactivation drives autophagy-dependent inflammasome activation in myeloid cells"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7491-2596","authenticated-orcid":true,"given":"Yung-Hsuan","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Molecular Biology, Academia Sinica, Taipei 11529, 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