{"doi":"10.1101/2022.11.22.517543","title":"IFNγ drives neuroinflammation and demyelination in a mouse model of multiple system atrophy","abstract":"Abstract Multiple system atrophy (MSA) is a rare and fatal synucleinopathy characterized by insoluble alpha-synuclein (α-syn) cytoplasmic inclusions located within oligodendroglia. Neuroinflammation, demyelination, and neurodegeneration are correlated with areas of GCI pathology, however it is not known what specifically drives disease pathogenesis. Recently in a mouse model of MSA, CD4+ T cells have been shown to drive neuroinflammation and demyelination, however the mechanism by which this occurs also remains unclear. In this study we use genetic and pharmacological approaches in a novel model of MSA to show that the pro-inflammatory cytokine interferon gamma (IFNγ) drives neuroinflammation and demyelination. Furthermore, using an IFNγ reporter mouse, we found that infiltrating CD4+ T cells were the primary producers of IFNγ in response to α-syn overexpression in oligodendrocytes. Results from these studies indicate that IFNγ expression in CD4 T cells drives α-syn-mediated neuroinflammation and demyelination, and strategies to target IFNγ expression may be a potential disease modifying therapeutic strategy for MSA.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":313272,"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":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493946,"name":"Gabrielle Childers","orcid":"0000-0003-1195-4750","position":1,"is_corresponding":false},{"id":1011981,"name":"Jhodi M. Webster","orcid":null,"position":2,"is_corresponding":false},{"id":1011982,"name":"Asta Zane","orcid":null,"position":3,"is_corresponding":false},{"id":1011508,"name":"Yating Yang","orcid":"0000-0001-5207-6742","position":4,"is_corresponding":false},{"id":1011983,"name":"Nikhita Mudium","orcid":null,"position":5,"is_corresponding":false},{"id":495697,"name":"Fredric P. Manfredsson","orcid":"0000-0001-5802-5487","position":6,"is_corresponding":false},{"id":504782,"name":"Jeffrey H. Kordower","orcid":"0000-0001-8629-3294","position":7,"is_corresponding":false},{"id":279113,"name":"Ashley S. Harms","orcid":"0000-0002-7054-2812","position":8,"is_corresponding":false},{"id":619755,"name":"Nicole J Gallups","orcid":null,"position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:33:44.454239Z","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":[]}