{"doi":"10.1084/jem.20201466","title":"Neutrophil-specific gain-of-function mutations in <i>Nlrp3</i> promote development of cryopyrin-associated periodic syndrome","abstract":"Gain-of-function mutations in NLRP3 are responsible for a spectrum of autoinflammatory diseases collectively referred to as \"cryopyrin-associated periodic syndromes\" (CAPS). Treatment of CAPS patients with IL-1-targeted therapies is effective, confirming a central pathogenic role for IL-1β. However, the specific myeloid cell population(s) exhibiting inflammasome activity and sustained IL-1β production in CAPS remains elusive. Previous reports suggested an important role for mast cells (MCs) in this process. Here, we report that, in mice, gain-of-function mutations in Nlrp3 restricted to neutrophils, and to a lesser extent macrophages/dendritic cells, but not MCs, are sufficient to trigger severe CAPS. Furthermore, in patients with clinically established CAPS, we show that skin-infiltrating neutrophils represent a substantial biological source of IL-1β. Together, our data indicate that neutrophils, rather than MCs, can represent the main cellular drivers of CAPS pathology.","journal":"The Journal of Experimental Medicine","year":2021,"id":158189,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":47,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.944,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":308013,"name":"Nicolas Gaudenzio","orcid":"0000-0002-5648-509X","position":1,"is_corresponding":false},{"id":666590,"name":"Nadine Serhan","orcid":"0000-0001-9870-9875","position":2,"is_corresponding":false},{"id":632302,"name":"Eva Conde","orcid":"0000-0002-5545-7054","position":3,"is_corresponding":false},{"id":666591,"name":"Ophélie Godon","orcid":"0000-0003-1511-3764","position":4,"is_corresponding":false},{"id":308011,"name":"Thomas Marichal","orcid":"0000-0003-1688-6291","position":5,"is_corresponding":false},{"id":308006,"name":"Philipp Starkl","orcid":"0000-0001-7521-129X","position":6,"is_corresponding":false},{"id":632303,"name":"Bianca Balbino","orcid":"0000-0002-0676-3012","position":7,"is_corresponding":false},{"id":666592,"name":"Axel Roers","orcid":"0000-0003-1806-6158","position":8,"is_corresponding":false},{"id":632315,"name":"Pierre Bruhns","orcid":"0000-0002-4709-8936","position":9,"is_corresponding":false},{"id":666593,"name":"Friederike Jönsson","orcid":"0000-0002-1667-8065","position":10,"is_corresponding":false},{"id":666594,"name":"Philippe Moguelet","orcid":"0000-0003-1996-6406","position":11,"is_corresponding":false},{"id":302230,"name":"Sophie Georgin‐Lavialle","orcid":"0000-0001-6668-8854","position":12,"is_corresponding":false},{"id":339566,"name":"Lori Broderick","orcid":"0000-0001-6147-7097","position":13,"is_corresponding":false},{"id":226040,"name":"Hal M. Hoffman","orcid":"0000-0001-8609-2548","position":14,"is_corresponding":false},{"id":73046,"name":"Stephen J. Galli","orcid":"0000-0001-5736-5340","position":15,"is_corresponding":false},{"id":308012,"name":"Laurent L. Reber","orcid":"0000-0003-3384-6769","position":16,"is_corresponding":false},{"id":632305,"name":"Julien Stackowicz","orcid":"0000-0001-6793-2855","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-18T23:44:26.210708Z","pmid":"34477811","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}