{"doi":"10.17615/0eds-1n25","title":"Defects in lysosomal maturation facilitate the activation of innate sensors in systemic lupus erythematosus","abstract":"Activation of innate sensors by self-antigen contributes to autoimmunity, although how intracellular sensors are chronically exposed to self-antigen has remained unknown. Here, we identify a previously unidentified defect in which lupus-prone macrophages fail to mature the lysosome, promoting the accumulation of apoptotic debris-containing IgG–immune complexes (IgG-ICs). Interestingly, macrophages from other autoimmune diseases accumulate IgG-ICs, indicating that lysosomal defects may underlie multiple autoimmune diseases. Furthermore, the prolonged intracellular residency chronically activates Toll-like receptors and permeabilizes the phagolysosomal membrane, allowing activation of cytosolic sensors. These findings identify lysosomal maturation as a unique defect in MRL/lpr mice that impacts multiple events known to underlie SLE, including pathogenic cytokine secretion.","journal":"UNC Libraries","year":2020,"id":135054,"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":0.9488,"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":520636,"name":"M. Joseph Costello","orcid":"0000-0003-0207-660X","position":1,"is_corresponding":false},{"id":546748,"name":"Andrew J. Monteith","orcid":"0000-0002-7259-6574","position":2,"is_corresponding":false},{"id":590584,"name":"Eric L. Scott","orcid":"0000-0001-5237-9794","position":3,"is_corresponding":false},{"id":547427,"name":"Sunah Kang","orcid":null,"position":4,"is_corresponding":false},{"id":275084,"name":"Barbara J. Vilen","orcid":"0000-0003-0014-0022","position":5,"is_corresponding":false},{"id":395815,"name":"Zenon Rajfur","orcid":"0000-0003-1265-6480","position":6,"is_corresponding":false},{"id":590585,"name":"Kai Hillman","orcid":"0000-0003-3393-6633","position":7,"is_corresponding":false},{"id":233845,"name":"Kenneth A. Jacobson","orcid":"0000-0001-8104-1493","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:27.963294Z","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":[]}