{"doi":"10.1101/2024.03.08.582968","title":"IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer’s disease","abstract":"Summary The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D:IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimer’s Disease, notably apolipoprotein-e . Lastly, using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 as a target of IRF3 that is relevant across various neuroinflammatory disorders. Together, our results identify IRF3 as an important regulator of LPS-mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":485997,"datarank":0.24141568686511508,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.0,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9575,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1201617,"name":"Veronika Brezáni","orcid":"0000-0003-2980-6334","position":1,"is_corresponding":false},{"id":968719,"name":"Gabrielle M. Mey","orcid":"0000-0002-3952-849X","position":2,"is_corresponding":false},{"id":899411,"name":"Sergi Guixé‐Muntet","orcid":"0000-0002-5748-1074","position":3,"is_corresponding":false},{"id":1126979,"name":"Martí Ortega‐Ribera","orcid":"0000-0001-8647-7069","position":4,"is_corresponding":false},{"id":672191,"name":"Yuan Zhuang","orcid":"0009-0005-4955-7146","position":5,"is_corresponding":false},{"id":1047013,"name":"Adam Zivny","orcid":null,"position":6,"is_corresponding":false},{"id":817085,"name":"Sebastian Werneburg","orcid":"0000-0002-2173-8392","position":7,"is_corresponding":false},{"id":891639,"name":"Jordi Gracia‐Sancho","orcid":"0000-0001-7736-4089","position":8,"is_corresponding":false},{"id":79619,"name":"Gyöngyi Szabó","orcid":"0000-0003-0836-2527","position":9,"is_corresponding":false},{"id":91419,"name":"Radhika Joshi","orcid":"0000-0002-4313-2586","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:07:57.049469Z","pmid":"38654824","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":[]}