{"doi":"10.1016/j.celrep.2025.115479","title":"Pyroptosis of pulmonary fibroblasts and macrophages through NLRC4 inflammasome leads to acute respiratory failure","abstract":"The NAIP/NLRC4 inflammasome plays a pivotal role in the defense against bacterial infections, with its in vivo physiological function primarily recognized as driving inflammation in immune cells. Acute lung injury (ALI) is a leading cause of mortality in sepsis. In this study, we identify that the NAIP/NLRC4 inflammasome is highly expressed in both macrophages and pulmonary fibroblasts and that pyroptosis of these cells plays a critical role in lung injury. Mice challenged with gram-negative bacteria or flagellin developed lethal lung injury, characterized by reduced blood oxygen saturation, disrupted lung barrier function, and escalated inflammation. Flagellin-induced lung injury was protected in caspase-1 or GSDMD-deficient mice. These findings enhance our understanding of the NAIP/NLRC4 inflammasome's (patho)physiological function and highlight the significant role of inflammasome activation and pyroptosis in ALI during sepsis.","journal":"Cell Reports","year":2025,"id":515929,"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":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9577,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":574963,"name":"Guoying Zhang","orcid":"0000-0001-9568-3702","position":1,"is_corresponding":false},{"id":829677,"name":"Brittany Dong","orcid":null,"position":2,"is_corresponding":false},{"id":517377,"name":"Ankit Pandeya","orcid":"0000-0002-7433-3129","position":3,"is_corresponding":false},{"id":574964,"name":"Jian Cui","orcid":"0000-0002-8483-9975","position":4,"is_corresponding":false},{"id":1024448,"name":"Samuel Santos Valença","orcid":"0000-0002-1868-9905","position":5,"is_corresponding":false},{"id":632851,"name":"Ling Yang","orcid":"0009-0006-3974-6100","position":6,"is_corresponding":false},{"id":1371761,"name":"Jiaqian Qi","orcid":"0000-0002-1613-4877","position":7,"is_corresponding":false},{"id":1367453,"name":"Zhuodong Chai","orcid":null,"position":8,"is_corresponding":false},{"id":376696,"name":"Congqing Wu","orcid":"0000-0001-7725-7881","position":9,"is_corresponding":false},{"id":337254,"name":"Daniel Kirchhofer","orcid":"0000-0002-0975-4402","position":10,"is_corresponding":false},{"id":458953,"name":"Toshihiko Shiroishi","orcid":"0000-0003-0535-2016","position":11,"is_corresponding":false},{"id":348616,"name":"Fadi T. Khasawneh","orcid":"0000-0002-4027-2997","position":12,"is_corresponding":false},{"id":651313,"name":"Min Tao","orcid":"0000-0003-4139-7596","position":13,"is_corresponding":false},{"id":218525,"name":"Feng Shao","orcid":"0000-0002-9562-7791","position":14,"is_corresponding":false},{"id":400506,"name":"Christopher M. Waters","orcid":"0000-0003-2336-7836","position":15,"is_corresponding":false},{"id":517379,"name":"Yinan Wei","orcid":"0000-0002-9936-7149","position":16,"is_corresponding":false},{"id":1380812,"name":"Zhenyu Li","orcid":"0009-0008-2180-1751","position":17,"is_corresponding":false},{"id":376695,"name":"Yan Zhang","orcid":"0000-0003-0472-3399","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:48:44.647022Z","pmid":"40158217","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":[]}