{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T01:02:08Z","timestamp":1781830928917,"version":"3.54.5"},"reference-count":48,"publisher":"Life Science Alliance, LLC","issue":"1","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["life-science-alliance.org"],"crossmark-restriction":true},"short-container-title":["Life Sci. Alliance"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Activating germline mutations in the human inflammasome sensor NLRP1 causes palmoplantar dyskeratosis and susceptibility to Mendelian autoinflammatory diseases. Recent studies have shown that the cytosolic serine dipeptidyl peptidases DPP8 and DPP9 suppress inflammasome activation upstream of NLRP1 and CARD8 in human keratinocytes and peripheral blood mononuclear cells. Moreover, pharmacological inhibition of DPP8\/DPP9 protease activity was shown to induce pyroptosis in murine C57BL\/6 macrophages without eliciting other inflammasome hallmark responses. Here, we show that DPP8\/DPP9 inhibition in macrophages that express a <jats:italic>Bacillus anthracis<\/jats:italic> lethal toxin (LeTx)\u2013sensitive <jats:italic>Nlrp1b<\/jats:italic> allele triggered significantly accelerated pyroptosis concomitant with caspase-1 maturation, ASC speck assembly, and secretion of mature IL-1\u03b2 and IL-18. Genetic ablation of ASC prevented DPP8\/DPP9 inhibition-induced caspase-1 maturation and partially hampered pyroptosis and inflammasome-dependent cytokine release, whereas deletion of caspase-1 or gasdermin D triggered apoptosis in the absence of IL-1\u03b2 and IL-18 secretion. In conclusion, blockade of DPP8\/DPP9 protease activity triggers rapid pyroptosis and canonical inflammasome hallmarks in primary macrophages that express a LeTx-responsive <jats:italic>Nlrp1b<\/jats:italic> allele.<\/jats:p>","DOI":"10.26508\/lsa.201900313","type":"journal-article","created":{"date-parts":[[2019,2,4]],"date-time":"2019-02-04T18:55:24Z","timestamp":1549306524000},"page":"e201900313","update-policy":"https:\/\/doi.org\/10.26508\/lsa.crossmarkpolicy","source":"Crossref","is-referenced-by-count":57,"title":["DPP8\/DPP9 inhibition elicits canonical Nlrp1b inflammasome hallmarks in murine macrophages"],"prefix":"10.26508","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7169-6602","authenticated-orcid":true,"given":"Nathalia M","family":"de Vasconcelos","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Ghent University, Ghent, Belgium"},{"name":"VIB-UGhent Center for Inflammation Research, VIB, Ghent, 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