{"doi":"10.1186/s12974-025-03496-2","title":"CXCR4 and CXCR6 dually limit T cell entry into the polyomavirus-infected brain","abstract":"T cell responses are vital for controlling viral infection in the central nervous system (CNS), but must be tightly regulated to limit tissue-damaging inflammation. Using mouse polyomavirus (MuPyV) CNS infection, an in vivo model for JCPyV-induced Progressive Multifocal Leukoencephalopathy (PML), we investigated sites of early infection, immune responses, and recruitment of T cells to the brain. Multiplexed error-robust fluorescence in situ hybridization (MERFISH) single-cell spatial transcriptomics was applied to assess the regionality of virus infection and brain-resident cell and infiltrating leukocyte responses. MERFISH, immunofluorescence microscopy, quantitative PCR, and flow cytometry demonstrate that the ependyma is the predominant region of MuPyV CNS infection and localization of T cells, and implicated CXCR4 and CXCR6 in T cell migration to the ependyma and subventricular zone. Using CXCR6 knockout mice and a specific CXCR4 small molecule antagonist, we found that the combined impairment of CXCR6 and CXCR4 signaling resulted in elevated infiltration of T cells in the MuPyV-infected brain. This work demonstrates that CXCR4 and CXCR6 act in a nonredundant fashion to restrict T cell accumulation to the polyomavirus-infected ependyma, with important implications for ongoing efforts to use JCPyV-specific T cell adoptive immunotherapy for PML.","journal":"Journal of Neuroinflammation","year":2025,"id":531561,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"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":1411791,"name":"Elia Afanasiev","orcid":"0000-0002-6527-4550","position":1,"is_corresponding":false},{"id":1317564,"name":"Arrienne B. Butic","orcid":"0000-0001-5991-7305","position":2,"is_corresponding":false},{"id":913615,"name":"Ge Jin","orcid":"0000-0002-9427-4023","position":3,"is_corresponding":false},{"id":1356967,"name":"Mofida Abdelmageed","orcid":"0000-0001-9507-4296","position":4,"is_corresponding":false},{"id":322311,"name":"Anirban Paul","orcid":"0000-0001-5347-9260","position":5,"is_corresponding":false},{"id":325882,"name":"Jo Anne Stratton","orcid":"0000-0002-1205-1353","position":6,"is_corresponding":false},{"id":913618,"name":"Aron E. Lukacher","orcid":"0000-0002-7969-2841","position":7,"is_corresponding":false},{"id":383775,"name":"Samantha A. Spencer","orcid":"0000-0001-5048-1736","position":8,"is_corresponding":false},{"id":1330347,"name":"Kalynn M Alexander","orcid":"0000-0001-8749-5744","position":0,"is_corresponding":true}],"reference_count":81,"raw_metadata":null,"created_at":"2026-07-19T02:51:14.579161Z","pmid":"40581668","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":[]}