Comparative Analysis of NZBxNZW F1 and FcgR2bKO mouse models of SLE 9046

Abstract Description Systemic Lupus Erythematosus (SLE) mouse models, including the NZBxNZW F1 model, reflect 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 NZBxNZW F1 mouse model to the FcγR2bKO mouse model for lupus, aiming to find similarities and differences in their expression profiles and renal pathology. 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. In contrast, NZBxNZW F1 mice have mostly subepithelial glomerular deposits and only rare subendothelial deposits. 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. 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. Topic Categories Basic Autoimmunity (BA)