{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Miglioranza Scavuzzi B"],"funding":["Intramural NIH HHS","U.S. Department of Health & Human Services | NIH | National Institute of Environmental Health Sciences","U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases","NIAMS NIH HHS"],"pagination":["751"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9334592"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["5(1)"],"pubmed_abstract":["The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble hum"],"journal":["Communications biology"],"pubmed_title":["The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope."],"pmcid":["PMC9334592"],"funding_grant_id":["HHSN273201600123P","R01AR059085","ES101074","R01 AR059085","T32AR07080","R33AR073014","T32 AR007080","R33 AR073014","R61AR073014","R01 AR074930","Z01 ES101074","R61 AR073014"],"pubmed_authors":["Miglioranza Scavuzzi B","Kahlenberg JM","Liu J","Mesquita-Ferrari RA","Farkash EA","Holoshitz J","van Drongelen V","Miller FW","Benavides F","Kaur B","Fox JC","Sawalha AH"],"additional_accession":[]},"is_claimable":false,"name":"The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope.","description":"The HLA-DRB1*03:01 allele is a major genetic risk factor in systemic lupus erythematosus (SLE), but the mechanistic basis of the association is unclear. Here we show that in the presence of interferon gamma (IFN-γ), a short DRB1*03:01-encoded allelic epitope activates a characteristic lupus transcriptome in mouse and human macrophages. It also triggers a cascade of SLE-associated cellular aberrations, including endoplasmic reticulum stress, unfolded protein response, mitochondrial dysfunction, necroptotic cell death, and production of pro-inflammatory cytokines. Parenteral administration of IFN-γ to naïve DRB1*03:01 transgenic mice causes increased serum levels of anti-double stranded DNA antibodies, glomerular immune complex deposition and histopathological renal changes that resemble hum","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-07-14T15:08:57.39Z","creation":"2025-04-19T22:47:17.633Z"},"accession":"S-EPMC9334592","cross_references":{"pubmed":["35902632"],"doi":["10.1038/s42003-022-03717-x"]}}