{"doi":"10.1101/2020.06.10.144956","title":"CD11c <sup>+</sup> CD88 <sup>+</sup> CD317 <sup>+</sup> myeloid cells are critical mediators of persistent CNS autoimmunity","abstract":"Abstract Background Natalizumab, a humanized monoclonal antibody (mAb) against α4-integrin, reduces the number of dendritic cells (DC) in cerebral perivascular spaces in multiple sclerosis (MS). Selective deletion of α4-integrin in CD11c + cells should curtail their migration to the CNS and ameliorate experimental autoimmune encephalomyelitis (EAE). Methods We generated CD11c.Cre +/- ITGA4 fl/fl C57/Bl6 mice to selectively delete α4-integrin in CD11c + cells. Active immunization and adoptive transfer EAE models were employed. Multi-parameter flow cytometry was utilized to immunophenotype leukocytes. Single-cell RNA sequencing (scRNA-seq) was used to profile individual cells. Results α4-integrin expression by CD11c + cells was significantly reduced in primary and secondary lymphoid organs in CD11c.Cre +/- ITGA4 fl/fl mice. In active EAE, a delayed disease onset was observed in CD11c.Cre +/- ITGA4 fl/fl mice, during which CD11c + CD88 + cells were sequestered in the blood. Upon EAE onset, CD11c + CD88 + cells accumulated in the CNS and expressed CD317 + . In adoptive transfer experiments, CD11c.Cre +/- ITGA4 fl/fl mice had ameliorated clinical disease associated with diminished numbers of CNS CD11c + CD88 + CD317 + cells. The transcription profile of CD11c + CD88 + CD317 + cells placed them within previously defined microglia-like cells in human CSF. We show that activated, but not naïve microglia expressed CD11c, CD88, and CD317. Finally, anti-CD317 treatment prior to clinical EAE substantially enhanced recovery. Conclusion CD11c + CD88 + CD317 + cells in the CNS promote inflammatory damage. Transcriptional analysis identifies CD11c + CD88 + CD317 + cells as a unique myeloid subset in human CSF. The disease-propagating effects of these cells can be antagonized using anti-CD317 mAb.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":130117,"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":0.9638,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":582387,"name":"Rehana Z. Hussain","orcid":"0000-0002-7700-913X","position":1,"is_corresponding":false},{"id":126593,"name":"Petra D. Cravens","orcid":null,"position":2,"is_corresponding":false},{"id":278786,"name":"Brian T. Edelson","orcid":"0000-0003-2856-7650","position":3,"is_corresponding":false},{"id":278785,"name":"Gregory F. Wu","orcid":"0000-0003-3588-0637","position":4,"is_corresponding":false},{"id":95053,"name":"Anne H. Cross","orcid":"0000-0003-0829-7569","position":5,"is_corresponding":false},{"id":582924,"name":"Richard Doelger","orcid":null,"position":6,"is_corresponding":false},{"id":582388,"name":"Nicolas Loof","orcid":"0000-0002-3362-5344","position":7,"is_corresponding":false},{"id":235695,"name":"Todd N. Eagar","orcid":"0000-0002-9738-544X","position":8,"is_corresponding":false},{"id":243603,"name":"Thomas G. Forsthuber","orcid":null,"position":9,"is_corresponding":false},{"id":582389,"name":"Laurent Calvier","orcid":"0000-0001-6437-2119","position":10,"is_corresponding":false},{"id":245969,"name":"Joachim Herz","orcid":"0000-0002-8506-3400","position":11,"is_corresponding":false},{"id":459927,"name":"Olaf Stüve","orcid":"0000-0002-0469-6872","position":12,"is_corresponding":false},{"id":582386,"name":"Navid Manouchehri","orcid":"0000-0001-5773-2622","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-18T23:15:53.196774Z","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":[]}