Esculentoside A alleviates lupus nephritis by modulating MAIT cells in MRL/lpr mice

Abstract

Introduction

This study aims to investigate the protective effect of esculentoside A (EsA) on lupus nephritis (LN) by modulating the mucosal-associated invariant T (MAIT) cells and associated cytokines in the renal tissue of MRL/lpr mice.

Methods

Eighteen 16-week-old female MRL/lpr mice were randomly assigned into the model and EsA groups (9 mice each), and 9 age-matched female Balb/c mice were included as a normal group. Mice were administered 0.2 mL of EsA solution (2.5 mg/mL) or RPMI 1640 medium (for control groups) via intraperitoneal injection once daily for 4 weeks. Urine protein/creatinine ratio (URCR) and blood creatinine (Cr) concentration were measured, Hematoxylin-eosin and Masson staining of renal tissues were performed, and the “Austin” acute index (AI) system for LN was determined and the protein expression of TNF-α, IFN-γ, IL-2, and IL-17 were assessed by Western blot. The proportion of MAIT cells in kidney tissues was analyzed using flow cytometry. Pearson correlation analysis was performed between renal MAIT cells and the expression of TNF-α, IFN-γ, IL-2, and IL-17 proteins in kidney tissues. Data were analyzed with SPSS 26.0 software.

Results

Compared with the normal group, the model group exhibited significantly elevated levels of Cr, UCPR, renal expression of TNF-α, IFN-γ, and IL-17, as well as an increased proportion of MAIT cells, along with the most severe renal histopathological damage and the highest AI score. In contrast, the EsA group showed a notable reduction in these parameters, although they remained elevated compared to the normal group. Kidney IL-2 expression was significantly lower in the model group than in the normal group, while EsA treatment resulted in an increase in IL-2 levels. Renal MAIT cells were positively correlated with TNF-α, IFN-γ, and IL-17 expression but negatively correlated with IL-2.

Discussion

EsA confers protection against LN in MRL/lpr mice by downregulating the proportion of MAIT cells in kidney tissue, reducing the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-17), and increasing IL-2 expression.