{"doi":"10.1101/2025.05.22.655368","title":"Effect of Age on Xenobiotic-Induced Autoimmunity","abstract":"Abstract Aging is associated with increased spontaneous autoantibody production and chronic inflammation, yet its impact on xenobiotic-induced autoimmunity remains unexplored. This study investigates the effect of age on mercury-induced autoimmunity (HgIA) in B10.S mice, a model of xenobiotic-induced autoimmunity characterized by anti-nucleolar autoantibodies (ANoA). Mature (3 months), adult (6 months), middle-aged (12 months), and old-age (24 months) mice were exposed to mercury (HgCl₂) or phosphate-buffered saline (PBS) for 4–5 weeks. While spontaneous anti-nuclear antibodies (ANA) increased with age in PBS-treated mice (34% in middle-aged, 57% in old age mice), HgIA incidence declined in old age mice, with only 59% (26/44) developing significant ANoA titers compared to 91–100% in younger cohorts. Notably, 56% (10/18) of initially ANoA-negative old mice had detectable ANoA at a lower dilution, indicating a reduced but not absent response. ANoA negativity in old age mice was associated with lower immunoglobulin levels, reduced anti-chromatin antibodies, and diminished germinal center formation, suggestive of immunosenescence. Flow cytometry revealed age-related declines in CD4⁺ T cells, with mercury exposure augmenting T-cell differentiation in younger but not old mice. These findings demonstrate that aging enhances spontaneous autoimmunity but impairs xenobiotic-induced autoimmunity, with a subset of old age mice retaining partial responsiveness at lower dilutions, highlighting the complex interplay between immunosenescence and environmental triggers.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558035,"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":0.9644,"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":335484,"name":"Amy K. Peiss","orcid":null,"position":1,"is_corresponding":false},{"id":1458490,"name":"Ho Yeung Leung","orcid":null,"position":2,"is_corresponding":false},{"id":1173284,"name":"Lisa Janssen","orcid":"0000-0002-8687-6745","position":3,"is_corresponding":false},{"id":135554,"name":"Dwight H. Kono","orcid":null,"position":4,"is_corresponding":false},{"id":333778,"name":"Jessica Mayeux","orcid":"0000-0001-7335-6807","position":5,"is_corresponding":false},{"id":135552,"name":"K. Michael Pollard","orcid":null,"position":6,"is_corresponding":false},{"id":1456039,"name":"Caroline de Ocampo","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40502004","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":[]}