Scientist Genentech south San Francisco, California, United States
Abstract Text: Systemic Lupus Erythematosus (SLE) mouse models, including the NZB/W F1 model, recapitulate key aspects of human disease pathology, involving dysregulation of various immune cell types such as B cells, T cells, dendritic cells, and macrophages. This study compared the NZWxNZB F1 mouse model to the FcγR2bKO mouse model for lupus, aiming to elucidate similarities and differences in their expression profiles and renal pathology. Transcriptomic analysis revealed distinct gene signatures, with the F1 model exhibiting a strong B cell signature and the FcγR2bKO model demonstrating an intriguing neutrophil signature. Histopathological examination of kidneys from the FcγR2bKO mice revealed features resembling stage 4 human lupus nephritis with extensive, large, subendothelial immune complex deposits and small, scattered, subepithelial deposits. TLR7 transgene was introduced to accelerate disease and the resulting TLR7Tg FcγR2bKO mice have an immature neutrophil population as well as neutrophil infiltration into the glomeruli. These findings highlight the utility of TLR7Tg FcγR2bKO mouse model in recapitulating aspects of lupus pathology and offer insights into the contribution neutrophils to disease pathogenesis.
