Lupus pathogenesis and autoimmunity are exacerbated by high fat diet-induced obesity in MRL/lpr mice

Abstract

ObjectiveSLE is an autoimmune disease characterised by persistent inflammation and autoantibody production. Genetic predisposition and environmental factors such as a high-fat diet (HFD) may contribute to lupus development. However, the immune cell profile and gender difference in response to HFD in lupus have not been reported. Here we investigated the impact of HFD on lupus pathogenesis and autoimmunity using lupus-prone mice.MethodsThirty male and 30 female MRL/lymphoproliferation (lpr) mice were fed with regular diet (RD) or HFD. Body weights were recorded weekly. SLE progression was monitored by skin lesion, urine protein, titres of antidouble-strand DNA (dsDNA) and ANA. At week 14, kidney and skin tissue sections were stained with H&E and periodic acid–Schiff to detect histological kidney index and skin score. Splenocytes were identified by immunofluorescence staining and flow cytometry.ResultsHFD significantly increased body weight and lipid levels compared with RD (p<0.01). Skin lesions were observed in 55.6% of the HFD group compared with 11.1% of the RD group, with greater histopathological skin scores in the female HFD group (p<0.01). Although both male and female mice had higher serum IgG in the HFD group than in the RD group, only the male HFD group showed an increased trend in anti-dsDNA Ab and ANA titres. Kidney pathological changes in the HFD group were more severe in male mice than in female mice (p<0.05), detected by proteinuria, kidney index and glomerular cell proliferation. Significant increases of germinal centre B cells and T follicular helper cells were observed in the spleens of HFD mice (p<0.05).ConclusionHFD induced an accelerated and exacerbated lupus development and autoimmunity in MRL/lpr mice. Our results parallel many known clinical lupus phenotypes and sexual dimorphism in which male patients are likelier to have a severe disease (nephritis) than female lupus patients who may have a broader range of lupus symptoms.

hUC-MSC transplantation therapy effects on lupus-prone MRL/lpr mice at early disease stages

“…The analysis of B cell subsets and the gate scheme in flow cytometry were performed according to previous reports (Fig. 3 A) [ 23 , 24 ]. Furthermore, to evaluate cell surface PD-L1 expression, hUC-MSCs were stained with Alexa Fluor 647-conjugated PD-L1 antibody (Additional file 1 : Fig.…”

“…Sections were stained with hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Masson’s trichrome stain, following a blind assessment by an experienced pathologist. The quantification of renal histopathological changes was performed as previously described in reference [ 23 , 24 ]. The scores assigned to mesangial proliferation and PAS + deposition ranged from 0 to 4, indicating the severity (0: absent; 1: mild; 2: mild-moderate; 3: moderate; 4: severe).…”