{"doi":"10.1101/2025.07.25.666876","title":"Aging-Associated Autoimmunity in Genetically Diverse UM-HET3 Mice Shows a Female Sex Bias","abstract":"Abstract C57BL/6 (B6) mice, often considered a non-autoimmune control strain, spontaneously develop autoantibodies and lymphocytic infiltration in the salivary glands (SG) with aging. However, as an inbred strain, B6 mice have a limited genetic background and do not fully represent a genetically diverse population. To assess whether genetic diversity influences the development of age-related autoimmunity, we studied UM-HET3 mice, a four-way cross that is commonly used in aging research. By 14–20 months of age, females showed significantly higher frequencies and endpoint titers of anti-nuclear antibodies. Older females also exhibited increased levels of splenic atypical/age-associated B cells and follicular helper T cells, populations associated with the production of autoantibodies. Similar immune cell changes were observed in the SG, with some female mice developing organized lymphocytic foci consisting of T and B cells. Our findings demonstrate that UM-HET3 mice naturally develop systemic autoimmunity and sialadenitis with age, with a clear female bias. Since female UM-HET3 mice have a longer median lifespan than males, these autoimmune responses may reflect benign autoimmunity, representing a heightened immune response associated with aging.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558623,"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":0.9583,"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":1223179,"name":"Magdalena Makuch","orcid":null,"position":1,"is_corresponding":false},{"id":1459456,"name":"Makayla Tillett","orcid":null,"position":2,"is_corresponding":false},{"id":415031,"name":"Harini Bagavant","orcid":null,"position":3,"is_corresponding":false},{"id":415032,"name":"Umesh S. Deshmukh","orcid":null,"position":4,"is_corresponding":false},{"id":1459455,"name":"Natalia Guzniczak","orcid":null,"position":0,"is_corresponding":true}],"reference_count":10,"raw_metadata":null,"created_at":"2026-07-19T02:55:25.969263Z","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":[]}