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- W4288077421 abstract "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 human lupus nephritis. This study provides evidence for a noncanonical, antigen presentation-independent mechanism of HLA-disease association in SLE and could lay new foundations for our understanding of key molecular mechanisms that trigger and propagate this devastating autoimmune disease." @default.
- W4288077421 created "2022-07-28" @default.
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- W4288077421 date "2022-07-28" @default.
- W4288077421 modified "2023-10-16" @default.
- W4288077421 title "The lupus susceptibility allele DRB1*03:01 encodes a disease-driving epitope" @default.
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- W4288077421 doi "https://doi.org/10.1038/s42003-022-03717-x" @default.
- W4288077421 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35902632" @default.
- W4288077421 hasPublicationYear "2022" @default.
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