{"doi":"10.3389/fimmu.2020.00230","title":"A Novel Microglia-Specific Transcriptional Signature Correlates With Behavioral Deficits in Neuropsychiatric Lupus","abstract":"Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) affect over one-half of SLE patients, yet underlying mechanisms remain largely unknown. We demonstrate that SLE-prone mice (CReCOM) develop NP-SLE, including behavioral deficits prior to systemic autoimmunity, reduced brain volumes, decreased vascular integrity, and brain-infiltrating leukocytes. NP-SLE microglia exhibit numerical expansion, increased synaptic uptake, and a more metabolically active phenotype. Microglia from multiple SLE-prone models express a \"NP-SLE signature\" unrelated to type I interferon. Rather, the signature is associated with lipid metabolism, scavenger receptor activity and downregulation of inflammatory and chemotaxis processes, suggesting a more regulatory, anti-inflammatory profile. NP-SLE microglia also express genes associated with disease-associated microglia (DAM), a subset of microglia thought to be instrumental in neurodegenerative diseases. Further, expression of \"NP-SLE\" and \"DAM\" signatures correlate with the severity of behavioral deficits in young SLE-prone mice prior to overt systemic disease. Our data are the first to demonstrate the predictive value of our newly identified microglia-specific \"NP-SLE\" and \"DAM\" signatures as a surrogate for NP-SLE clinical outcomes and suggests that microglia-intrinsic defects precede contributions from systemic SLE for neuropsychiatric manifestations.","journal":"Frontiers in Immunology","year":2020,"id":91046,"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":46,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9508,"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":456349,"name":"Deborah R. Winter","orcid":"0000-0003-1806-673X","position":1,"is_corresponding":false},{"id":334773,"name":"Daniele Procissi","orcid":"0000-0001-5350-0170","position":2,"is_corresponding":false},{"id":456350,"name":"Elise V. Mike","orcid":"0000-0002-5913-4332","position":3,"is_corresponding":false},{"id":457835,"name":"Ariel Stock","orcid":null,"position":4,"is_corresponding":false},{"id":457836,"name":"Mary J. Kando","orcid":null,"position":5,"is_corresponding":false},{"id":456351,"name":"Gaurav Gadhvi","orcid":"0000-0002-4379-2824","position":6,"is_corresponding":false},{"id":457837,"name":"Steven Droho","orcid":null,"position":7,"is_corresponding":false},{"id":456352,"name":"Christina L. Bloomfield","orcid":"0000-0002-6012-3745","position":8,"is_corresponding":false},{"id":456353,"name":"Salina Dominguez","orcid":"0009-0002-2659-7610","position":9,"is_corresponding":false},{"id":457838,"name":"Maximilian G. Mayr","orcid":null,"position":10,"is_corresponding":false},{"id":456354,"name":"Jeremy A. Lavine","orcid":"0000-0002-0884-1336","position":11,"is_corresponding":false},{"id":278765,"name":"Chaim Putterman","orcid":"0000-0002-3204-6068","position":12,"is_corresponding":false},{"id":456355,"name":"Carla M. Cuda","orcid":"0000-0002-2022-8171","position":13,"is_corresponding":false},{"id":456348,"name":"Hadijat M. Makinde","orcid":"0000-0001-8492-4187","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-18T22:28:45.409789Z","pmid":"32174913","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":[]}