Dysregulation of T follicular cells and antibody responses in high fat-diet associated lupus development in MRL/lpr mice

Abstract

Abstract Background/Purpose Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by persistent inflammation, autoantibodies production, and organ damage. Genetic predisposition and environmental factors such as fat diet/obesity contribute to lupus pathogenesis. Here, we investigated the role of immune cells, especially T follicular helper (Tfh) cells and T regulatory (Treg) cells, in bridging obesity and SLE manifestations using lupus prone mice. Methods Fifty MRL/lpr mice were fed and grouped in a regular diet (RD) or high fat diet (HFD). Body weights and skin lesions were recorded weekly. Urine protein, serum IgG, anti-dsDNA antibody (Ab), and anti-nuclear Ab were detected. At week 14, kidney and skin biopsy were collected for H&E and PAS staining for histopathological lesions and quantified as kidney index and skin score. Immune cells in spleen were examined by flow cytometry and confirmed by slides staining. Results HFD induced a significant increase in body weight than RD (p<0.01). SLE features, such as skin lesions, splenomegaly, proteinuria, higher kidney index, increase of anti-dsDNA Ab and IgG titer were observed in HFD mice. There were significant increase of germinal center B cells and plasma cells in the spleen of HFD mice. The percentage of Tfh cells and the ratio of Tfh/Treg were significantly increased in HFD group (p<0.05). Conclusion HFD induced an exacerbated lupus development with dysregulated Tfh/Treg cells associated with increased of anti-dsDNA Ab in MRL/lpr mice, suggesting the central role of Tfh/Treg cells in linking HFD to autoimmunity in SLE. Intervention of healthy diet or restoring balance of Tfh/Treg cells may improve lupus symptoms and outcomes in genetically predisposed individual. Supported by None