{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:33:27Z","timestamp":1789450407433,"version":"build-2803163510"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"75","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:p>\n                    Dipeptidyl peptidase 9 (DPP9) is a direct inhibitor of NLRP1, but how it affects inflammasome regulation in vivo is not yet established. Here, we report three families with immune-associated defects, poor growth, pancytopenia, and skin pigmentation abnormalities that segregate with biallelic\n                    <jats:italic>DPP9<\/jats:italic>\n                    rare variants. Using patient-derived primary cells and biochemical assays, these variants were shown to behave as hypomorphic or knockout alleles that failed to repress NLRP1. The removal of a single copy of\n                    <jats:italic>Nlrp1a\/b\/c<\/jats:italic>\n                    ,\n                    <jats:italic>Asc<\/jats:italic>\n                    ,\n                    <jats:italic>Gsdmd<\/jats:italic>\n                    , or\n                    <jats:italic>Il-1r<\/jats:italic>\n                    , but not\n                    <jats:italic>Il-18<\/jats:italic>\n                    , was sufficient to rescue the lethality of\n                    <jats:italic>Dpp9<\/jats:italic>\n                    mutant neonates in mice. Similarly,\n                    <jats:italic>dpp9<\/jats:italic>\n                    deficiency was partially rescued by the inactivation of\n                    <jats:italic>asc<\/jats:italic>\n                    , an obligate downstream adapter of the NLRP1 inflammasome, in zebrafish. These experiments suggest that the deleterious consequences of DPP9 deficiency were mostly driven by the aberrant activation of the canonical NLRP1 inflammasome and IL-1\u03b2 signaling. Collectively, our results delineate a Mendelian disorder of DPP9 deficiency driven by increased NLRP1 activity as demonstrated in patient cells and in two animal models of the disease.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.abi4611","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T13:57:15Z","timestamp":1663336635000},"source":"Crossref","is-referenced-by-count":50,"title":["DPP9 deficiency: An inflammasomopathy that can be rescued by lowering NLRP1\/IL-1 signaling"],"prefix":"10.1126","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8875-4645","authenticated-orcid":true,"given":"Cassandra R.","family":"Harapas","sequence":"first","affiliation":[{"name":"Inflammation Division, the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia."},{"name":"Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-8789","authenticated-orcid":true,"given":"Kim S.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Skin Research Institute of Singapore (SRIS), A*STAR, Singapore, Singapore."},{"name":"Skin Research Laboratories (ASRL), A*STAR, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8843-5567","authenticated-orcid":true,"given":"Kenneth","family":"Lay","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Therapeutics, Genome Institute of Singapore (GIS), A*STAR, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmine","family":"Wong","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Therapeutics, Genome Institute of Singapore (GIS), A*STAR, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2607-107X","authenticated-orcid":true,"given":"Ricardo","family":"Moreno Traspas","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Therapeutics, Genome Institute of Singapore (GIS), A*STAR, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrin","family":"Nabavizadeh","sequence":"additional","affiliation":[{"name":"Laboratory of Human Genetics and Therapeutics, Genome Institute of Singapore (GIS), A*STAR, Singapore, Singapore."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annick","family":"Rass-Rothschild","sequence":"additional","affiliation":[{"name":"the Institute for Rare Diseases, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5240-3555","authenticated-orcid":true,"given":"Bertrand","family":"Boisson","sequence":"additional","affiliation":[{"name":"St.\u00a0Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New\u00a0York, NY, USA."},{"name":"Paris University, Imagine Institute, Paris, France."},{"name":"Laboratory of Human Genetics of Infectious Disease, Necker Branch, INSERM U1163, Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Drutman","sequence":"additional","affiliation":[{"name":"St.\u00a0Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, the Rockefeller University, New\u00a0York, NY, 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Rockefeller Branch, the Rockefeller University, New\u00a0York, NY, USA."},{"name":"Paris University, Imagine Institute, Paris, France."},{"name":"Laboratory of Human Genetics of Infectious Disease, Necker Branch, INSERM U1163, Paris, France."},{"name":"Pediatric Immunology-Hematology Unit, Assistance Publique-H\u00f4pitaux de Paris, Necker Hospital for Sick Children, Paris, France."},{"name":"Howard Hughes Medical Institute, New\u00a0York, NY, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5369-346X","authenticated-orcid":true,"given":"Jonathan A.","family":"Bernstein","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0516-6021","authenticated-orcid":true,"given":"Franklin L.","family":"Zhong","sequence":"additional","affiliation":[{"name":"Skin Research 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Medicine (KUSOM), Istanbul, Turkey."},{"name":"Laboratory of Human Genetics and Therapeutics, Institute of Molecular and Cellular Biology (IMCB), A*STAR, Singapore, Singapore."},{"name":"Smart-Health Initiative, Biological and Environmental Sciences and Engineering Division, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi 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of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice","volume":"159","author":"Labow M.","year":"1997","unstructured":"M.\u00a0Labow, D.\u00a0Shuster, M.\u00a0Zetterstrom, P.\u00a0Nunes, R.\u00a0Terry, E. B.\u00a0Cullinan, T.\u00a0Bartfai, C.\u00a0Solorzano, L. L.\u00a0Moldawer, R.\u00a0Chizzonite, K. W.\u00a0McIntyre,Absence of IL-1 signaling and reduced inflammatory response in IL-1 type I receptor-deficient mice. J. Immunol.159,2452\u20132461 (1997).","journal-title":"J. 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