Sex disparities in pathological features and autoimmunity in high fat diet associated lupus mouse model

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is more common in women than men. SLE has been reported with diverse clinical phenotypes of varying severity, which may be caused by sex hormones and environmental factors. Our recent studies showed that high-fat diet (HFD) exacerbated lupus development in MRL/lpr lupus-prone mice. Here we explored the gender difference in lupus progress and autoimmune response to HFD. Twenty male and twenty female MRL/lpr mice were evenly grouped and fed with a regular diet (RD, 10% fat) or HFD (60% fat) for 14 weeks. Body weights were recorded weekly. SLE progression was monitored by skin lesions, urine protein, titers of anti-dsDNA antibody in serum. Kidney and skin from the dorsum of the neck were embedded for H&E, PAS, and Masson’s staining quantified as kidney index and skin score. Immune cells in the spleens were identified by immunofluorescence staining and flow cytometry. HFD induced a greater weight gain in female mice than male mice (p<0.01). Skin rash showed up as early as week 6 in female HFD group with a greater histopathological skin score (p<0.01). Splenomegaly, proteinuria, and anti-dsDNA level were increased only in male HFD group. Kidney pathological changes were more severe in male HFD mice with significant increase of kidney index (p<0.05). Significant increases of germinal center B cells, plasma cells, and T follicular helper cells were observed in HFD mice (p<0.05). SLE progression is sexually dimorphic in lupus-prone mice in response to HFD. Our results parallel many known clinical lupus phenotypes and sexual dimorphism in which male patients are more likely to have severe disease (such as nephritis) than female lupus patients who may have a broader range of lupus symptoms. None