{"doi":"10.1016/j.cell.2024.11.031","title":"Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes","abstract":"Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection. Lymphocytes become dependent on oxysterols, generated through a transcellular endothelial-fibroblast metabolic pathway, and the receptor EBI2 for inflamed LN entry. Additionally, Langerhans cells are an oxysterol source. Ch25h is also expressed in inflamed peripheral endothelium, and EBI2 mediates B cell recruitment in a tumor model. Finally, we demonstrate that LN CCL19 is critical in lymphocyte recruitment during inflammation. Thus, our work explains how naive precursor trafficking is sustained in responding LNs, identifies a role for oxysterols in cell recruitment into inflamed tissues, and establishes a logic for the CCR7 two-ligand system.","journal":"Cell","year":2024,"id":418746,"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":0.9525,"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":718220,"name":"Marco De Giovanni","orcid":"0000-0001-7521-3092","position":1,"is_corresponding":false},{"id":965889,"name":"Ying Xu","orcid":"0000-0001-9994-9889","position":2,"is_corresponding":false},{"id":385609,"name":"Jinping An","orcid":"0009-0009-5158-4505","position":3,"is_corresponding":false},{"id":1207248,"name":"Nikhita Kirthivasan","orcid":"0009-0005-4864-7799","position":4,"is_corresponding":false},{"id":728910,"name":"Erick Lu","orcid":"0000-0001-8175-5146","position":5,"is_corresponding":false},{"id":844373,"name":"Kan Jiang","orcid":"0000-0001-9065-4574","position":6,"is_corresponding":false},{"id":218255,"name":"Stephen R. Brooks","orcid":"0000-0001-5592-5332","position":7,"is_corresponding":false},{"id":348613,"name":"Serena Ranucci","orcid":"0000-0001-7177-2188","position":8,"is_corresponding":false},{"id":821807,"name":"Jiuling Yang","orcid":"0000-0002-5301-6976","position":9,"is_corresponding":false},{"id":1207249,"name":"Shuto Kanameishi","orcid":"0000-0002-1616-1349","position":10,"is_corresponding":false},{"id":313401,"name":"Kenji Kabashima","orcid":"0000-0002-0773-0554","position":11,"is_corresponding":false},{"id":106966,"name":"Kevin Brulois","orcid":"0000-0002-6024-6075","position":12,"is_corresponding":false},{"id":392260,"name":"Michael Bscheider","orcid":"0000-0001-7808-3270","position":13,"is_corresponding":false},{"id":246000,"name":"Eugene C. Butcher","orcid":"0000-0001-8786-7907","position":14,"is_corresponding":false},{"id":235419,"name":"Jason G. Cyster","orcid":"0000-0002-4735-9745","position":15,"is_corresponding":false},{"id":49572,"name":"Kevin Y. Chen","orcid":"0000-0001-5299-8368","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:57:09.067930Z","pmid":"39708807","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":[]}