{"doi":"10.1101/2025.05.28.656699","title":"L-selectin shedding regulates functional recovery and neutrophil clearance following spinal cord injury in a sex-dependent manner","abstract":"During the acute phase of spinal cord injury (SCI), neutrophils infiltrate in large numbers and can exacerbate inflammation, secondary tissue damage, and neurological deficits. L-selectin is a signaling and adhesion receptor that has been shown to facilitate neutrophil recruitment and secondary injury after SCI. During neutrophil activation, L-selectin is typically cleaved or shed from the cell surface and augmenting L-selectin shedding can improve hindlimb recovery and tissue sparing following SCI in male mice. However, it is unclear how endogenous L-selectin shedding regulates neutrophil responses and functional recovery after SCI, particularly when also considering sex as a biological variable. In this study, we investigated the sex-dependent role of endogenous L-selectin shedding in neutrophil function and long-term outcomes in a murine thoracic contusion model of SCI. We found that endogenous L-selectin shedding improves long-term functional recovery and white matter sparing in female, but not male, mice. In addition, we demonstrate that L-selectin shedding alters neutrophil accumulation in a sex-dependent manner. While L-selectin shedding does not mediate neutrophil activation or effector functions, we found that neutrophil clearance is facilitated by L-selectin shedding in female mice alone. These results demonstrate that endogenous L-selectin shedding is a critical and sex-dependent mediator of neutrophil accumulation and clearance, as well as long-term functional outcomes, after SCI.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":567242,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"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":1459072,"name":"Mia R. Pacheco","orcid":null,"position":1,"is_corresponding":false},{"id":724521,"name":"Shelby K. Reid","orcid":"0000-0002-8917-823X","position":2,"is_corresponding":false},{"id":481165,"name":"Victor Tseng","orcid":"0000-0003-1380-2240","position":3,"is_corresponding":false},{"id":725178,"name":"Megan A. Kirchhoff","orcid":null,"position":4,"is_corresponding":false},{"id":1471679,"name":"Sai Tadiboyina","orcid":null,"position":5,"is_corresponding":false},{"id":1471680,"name":"Donghun Min","orcid":null,"position":6,"is_corresponding":false},{"id":316860,"name":"Dylan A. McCreedy","orcid":"0000-0003-2413-0793","position":7,"is_corresponding":false},{"id":1386153,"name":"Miranda E. Leal-Garcia","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:56:44.340853Z","pmid":"40501839","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":[]}