{"doi":"10.1083/jcb.202404079","title":"Galectin-9 regulates dendritic cell polarity and uropod contraction by modulating RhoA activity","abstract":"Adaptive immunity relies on dendritic cell (DC) migration to transport antigens from tissues to lymph nodes. Galectins, a family of β-galactoside-binding proteins, control cell membrane organization, exerting crucial roles in multiple physiological processes. Here, we report a novel mechanism underlying cell polarity and uropod retraction by demonstrating that galectin-9 regulates basal and chemokine-driven DC migration in humans and mice. Galectin-9 depletion caused a defect in RhoA signaling that resulted in impaired cell rear contractility. Mechanistically, galectin-9 interacts with and organizes CD44 at the cell surface, in turn modulating RhoA binding to GEF-H1 and the initiation of downstream signaling. Analysis of DC motility in the 3D tumor microenvironment revealed galectin-9 is also required for DC recruitment and infiltration. Exogenous galectin-9 rescued the motility of tumor-immunocompromised human blood DCs, validating the physiological relevance of galectin-9 in DC migration. Our results identify galectin-9 as a necessary mechanistic component for DC motility by regulating cell polarity and contractility, and underscore its implications for DC-based immunotherapies.","journal":"The Journal of Cell Biology","year":2025,"id":547088,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9498,"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":1439099,"name":"Harry Warner","orcid":"0000-0003-2313-6974","position":1,"is_corresponding":false},{"id":1439100,"name":"Jorge Cuenca‐Escalona","orcid":"0000-0002-4915-1518","position":2,"is_corresponding":false},{"id":1255664,"name":"Isabel F. Stehle","orcid":"0009-0006-0957-5144","position":3,"is_corresponding":false},{"id":1439101,"name":"Vince P.A. van Reijmersdal","orcid":"0009-0005-2734-8247","position":4,"is_corresponding":false},{"id":1439521,"name":"Sophie E. Klomp","orcid":null,"position":5,"is_corresponding":false},{"id":1439522,"name":"Koert Schreurs","orcid":null,"position":6,"is_corresponding":false},{"id":1439102,"name":"Andrea Rodgers Furones","orcid":"0000-0002-0635-4470","position":7,"is_corresponding":false},{"id":1439103,"name":"Rohit Gokhale","orcid":"0000-0003-1555-1174","position":8,"is_corresponding":false},{"id":1439104,"name":"Manon Vullings","orcid":"0000-0002-9557-0406","position":9,"is_corresponding":false},{"id":1439105,"name":"René Classens","orcid":"0009-0004-0143-6030","position":10,"is_corresponding":false},{"id":1439106,"name":"Stefania Di Blasio","orcid":"0000-0002-7585-8277","position":11,"is_corresponding":false},{"id":1439107,"name":"Yusuf Dölen","orcid":"0000-0001-8211-9811","position":12,"is_corresponding":false},{"id":1439108,"name":"Sjoerd van Deventer","orcid":"0000-0001-8972-6665","position":13,"is_corresponding":false},{"id":556274,"name":"Katarina Wolf","orcid":"0000-0003-0616-2708","position":14,"is_corresponding":false},{"id":657413,"name":"Inge M. N. Wortel","orcid":"0000-0003-3362-5229","position":15,"is_corresponding":false},{"id":1439109,"name":"Joseph H. R. Hetmanski","orcid":"0000-0002-1493-351X","position":16,"is_corresponding":false},{"id":1439110,"name":"Annemiek B. van Spriel","orcid":"0000-0002-3590-2368","position":17,"is_corresponding":false},{"id":1439111,"name":"Laia Querol Cano","orcid":"0000-0002-7650-9407","position":18,"is_corresponding":false},{"id":1439520,"name":"Guus A. Franken","orcid":null,"position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40986321","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":[]}