{"doi":"10.1016/j.immuni.2025.02.003","title":"Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis","abstract":null,"journal":"Immunity","year":2025,"id":613744,"datarank":0.5456379239589579,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"self_citation_contribution":0.5456379239589579,"citation_network_contribution":0.0,"self_endowment_contribution":0.5456379239589579,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":37,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1581282,"name":"Yuchao Jing","orcid":null,"position":1,"is_corresponding":false},{"id":1392730,"name":"Juan He","orcid":"0000-0003-0199-3852","position":2,"is_corresponding":false},{"id":295619,"name":"Rui Dong","orcid":"0000-0003-0985-6211","position":3,"is_corresponding":false},{"id":1581284,"name":"Tongyang Li","orcid":null,"position":4,"is_corresponding":false},{"id":310298,"name":"Fang Li","orcid":"0000-0002-7617-6534","position":5,"is_corresponding":false},{"id":702311,"name":"Xiaoqing Zheng","orcid":"0000-0002-0365-4953","position":6,"is_corresponding":false},{"id":1581286,"name":"Gaoyu Liu","orcid":null,"position":7,"is_corresponding":false},{"id":1581287,"name":"Ran Jia","orcid":null,"position":8,"is_corresponding":false},{"id":432672,"name":"Jin Xu","orcid":"0000-0003-3072-1899","position":9,"is_corresponding":false},{"id":1401911,"name":"Fan Wu","orcid":"0000-0003-1845-437X","position":10,"is_corresponding":false},{"id":1581289,"name":"Chunhong Jia","orcid":null,"position":11,"is_corresponding":false},{"id":738915,"name":"Jin Song","orcid":"0000-0002-7733-6253","position":12,"is_corresponding":false},{"id":133964,"name":"Lijuan Zhang","orcid":null,"position":13,"is_corresponding":false},{"id":1581292,"name":"Pan Zhou","orcid":null,"position":14,"is_corresponding":false},{"id":1233255,"name":"Haitao Wang","orcid":"0000-0003-2340-0739","position":15,"is_corresponding":false},{"id":1033569,"name":"Zhi Yao","orcid":"0000-0002-9490-3870","position":16,"is_corresponding":false},{"id":416396,"name":"Qiang Liu","orcid":"0000-0003-1229-7908","position":17,"is_corresponding":false},{"id":569791,"name":"Ying Yu","orcid":"0009-0006-9903-6514","position":18,"is_corresponding":false},{"id":1468766,"name":"Jie Zhou","orcid":"0009-0009-5935-8051","position":19,"is_corresponding":false},{"id":1253645,"name":"Yuxin Zhang","orcid":"0000-0002-1826-3824","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis","abstract":"Necrotizing enterocolitis (NEC) is a common pediatric emergency primarily afflicting preterm infants, yet its mechanisms remain to be fully understood. Here, we report that plasma fibroblast growth factor (FGF)19, a target of farnesoid X receptor (FXR), was positively correlated with the clinical parameters of NEC. NEC patients and the NEC murine model displayed abundant FXR in intestinal epithelial cells (IECs), which was restricted by microbiota-derived short-chain fatty acids (SCFAs) under homeostasis. Genetic deficiency of FXR in IECs caused remission of NEC. Mechanistically, FXR facilitated ferroptosis of IECs via targeting acyl-coenzyme A synthetase long-chain family member 4 (Acsl4). Lipid peroxides released by ferroptotic IECs suppressed interleukin (IL)-22 secretion from type 3 innate lymphoid cells (ILC3s), thereby exacerbating NEC. Intestinal FXR antagonist, ACSL4 inhibitor, and ferroptosis inhibitor ameliorated murine NEC. Furthermore, the elevated lipid peroxides in NEC patients were positively correlated with FGF19 and disease parameters. These observations demonstrate the therapeutic value of targeting intestinal FXR and ferroptosis in NEC treatment.","is_dataset_classified":null,"base_score":3.6375861597263857,"endowment":3.6375861597263857,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40023163","pmcid":null,"openalex_id":"https://openalex.org/W4408028101","authors":[],"funders":[{"funder_name":"National Key Research and Development Program of China","grant_id":"2021ZD0202400","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82225015","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82001691","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82430055","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"81925018","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82130049","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82321001","title":null},{"funder_name":"National Natural Science Foundation of China","grant_id":"82488301","title":null}],"total_grants":8,"fwci":23.0104,"citation_percentile":0.99821078,"influential_citations":0,"citation_trend":[{"year":2025,"count":21},{"year":2026,"count":16}],"oa_status":"closed","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S1074761325000706?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1074761325000706?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.immuni.2025.02.003","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40023163","host_type":"repository"}],"fields_of_study":["Infant Nutrition and Health","Neonatal Respiratory Health Research","Congenital Diaphragmatic Hernia Studies","Animals","Ferroptosis","Humans","Enterocolitis, Necrotizing","Mice","Receptors, Cytoplasmic and Nuclear","Intestinal Mucosa","Infant, Newborn","Lymphocytes","Fibroblast Growth Factors","Disease Models, Animal","Mice, Inbred C57BL","Coenzyme A Ligases","Mice, Knockout","Female","Male","Immunity, Innate","Receptor, Farnesoid X-Activated"],"mesh_terms":["Ferroptosis","Receptor, Farnesoid X-Activated","Animals","Bile Acids and Salts","Coenzyme A Ligases","Disease Models, Animal","Epithelial Cells","Female","Fibroblast Growth Factors","Humans","Immunity, Innate","Infant, Newborn","Intestinal Mucosa","Lymphocytes","Male","Mice, Inbred C57BL","Receptors, Cytoplasmic and Nuclear","Mice, Knockout","Enterocolitis, Necrotizing","Mice"],"keywords":["Necrotizing enterocolitis","Biology","Bile acid","Farnesoid X receptor","Receptor","Enterocolitis","Internal medicine","Gastroenterology","Endocrinology","Nuclear receptor","Medicine","Biochemistry","Transcription factor","FXR","IECs","ILC3s","NEC","microbiota","neonatal intestine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T09:07:09.623866Z","pmid":null,"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":[]}