{"doi":"10.1038/s41598-024-52710-3","title":"Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) deletion in myeloid cells augments cholestatic liver injury","abstract":"Abstract Ductular reactive (DR) cells exacerbate cholestatic liver injury and fibrosis. Herein, we posit that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) emanates from recruited macrophages and restrains DR cell expansion, thereby limiting cholestatic liver injury. Wild type (WT), Trail fl/fl and myeloid-specific Trail deleted ( Trail Δmye ) C57BL/6 mice were exposed to DDC diet-induced cholestatic liver injury, which induced hepatomegaly and liver injury as compared to control diet-fed mice. However, parameters of liver injury, fibrosis, and inflammation were all increased in the Trail Δmye mice as compared to the WT and Trail fl/fl mice. High dimensional mass cytometry indicated that cholestasis resulted in increased hepatic recruitment of subsets of macrophages and neutrophils in the Trail Δmye mice. Spatial transcriptomics analysis revealed that the PanCK + cholangiocytes from Trail Δmye mice had increased expression of the known myeloid attractants S100a8, Cxcl5, Cx3cl1, and Cxcl1. Additionally, in situ hybridization of Cxcl1, a potent neutrophil chemoattractant, demonstrated an increased expression in CK19 + cholangiocytes of Trail Δmye mice. Collectively, these data suggest that TRAIL from myeloid cells, particularly macrophages, restrains a subset of DR cells (i.e., Cxcl1 positive cells), limiting liver inflammation and fibrosis. Reprogramming macrophages to express TRAIL may be salutary in cholestasis.","journal":"Scientific Reports","year":2024,"id":441816,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"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":374902,"name":"Nazlı Begüm Öztürk","orcid":"0000-0002-8595-1838","position":1,"is_corresponding":false},{"id":1255377,"name":"Kaiyel A. Cutshaw","orcid":null,"position":2,"is_corresponding":false},{"id":374900,"name":"Maria Eugenia Guicciardi","orcid":"0000-0003-4579-2753","position":3,"is_corresponding":false},{"id":1255378,"name":"Takashi Kitagataya","orcid":null,"position":4,"is_corresponding":false},{"id":1255379,"name":"Kirsta E. Olson","orcid":null,"position":5,"is_corresponding":false},{"id":230194,"name":"Kevin D. Pavelko","orcid":"0000-0001-7555-1315","position":6,"is_corresponding":false},{"id":1255380,"name":"William H. Sherman","orcid":null,"position":7,"is_corresponding":false},{"id":571486,"name":"Alexander Q. Wixom","orcid":"0000-0003-2982-7303","position":8,"is_corresponding":false},{"id":308490,"name":"Nidhi Jalan‐Sakrikar","orcid":"0000-0001-6795-0121","position":9,"is_corresponding":false},{"id":850196,"name":"Michelle Baez-Faria","orcid":null,"position":10,"is_corresponding":false},{"id":1254885,"name":"Florencia Gutiérrez","orcid":"0000-0002-6433-3440","position":11,"is_corresponding":false},{"id":243083,"name":"Gregory J. Gores","orcid":"0000-0003-3151-009X","position":12,"is_corresponding":false},{"id":250277,"name":"Anuradha Krishnan","orcid":"0000-0001-8467-6777","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:01:11.152920Z","pmid":"38273071","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":[]}