{"doi":"10.1016/j.celrep.2024.114685","title":"CD14 is a decision-maker between Fas-mediated death and inflammation","abstract":"Signaling through classical death receptor Fas was mainly appreciated as a pro-death pathway until recent reports characterized pro-inflammatory outcomes of Fas-mediated activation in pathological contexts. How Fas signaling can switch to pro-inflammatory activation is poorly understood. Herein, we report that in macrophages and neutrophils, the Toll-like receptor (TLR) adapter CD14 determines the inflammatory output of Fas-mediated signaling. Our findings propose CD14 as a crucial chaperone of Fas receptor internalization in macrophages and neutrophils, resulting in Cd14 −/− myeloid cells that are protected from FasL-induced apoptosis, activate nuclear factor κB (NF-κB), and release cytokines in response. As in TLR signaling, CD14 is also required for Fas to signal through the adaptor TRIF (TIR-domain-containing adapter-inducing interferon-β) and induce a pro-death complex. Our findings demonstrate that CD14 availability can determine the switch between Fas-mediated pro-death and pro-inflammatory outcomes by internalizing the receptor.","journal":"Cell Reports","year":2024,"id":438963,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9494,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":868980,"name":"David Jetton","orcid":"0000-0002-1615-9986","position":1,"is_corresponding":false},{"id":388580,"name":"Hayley I. Muendlein","orcid":"0000-0003-3006-5780","position":2,"is_corresponding":false},{"id":478235,"name":"Wilson M. Connolly","orcid":null,"position":3,"is_corresponding":false},{"id":1249567,"name":"Hunter Russell","orcid":null,"position":4,"is_corresponding":false},{"id":51938,"name":"Irina Smirnova","orcid":null,"position":5,"is_corresponding":false},{"id":286447,"name":"Shruti Sharma","orcid":"0000-0001-8200-108X","position":6,"is_corresponding":false},{"id":446788,"name":"Stephen C. Bunnell","orcid":"0000-0001-6887-0828","position":7,"is_corresponding":false},{"id":51936,"name":"Alexander Poltorak","orcid":"0000-0002-5375-6587","position":8,"is_corresponding":false},{"id":635007,"name":"Zoie Magri","orcid":"0000-0001-9378-4278","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:00:43.618468Z","pmid":"39213151","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":[]}