Celastrol alleviates murine lupus nephritis via inducting CD4+Foxp3+ regulatory T cells

INTRODUCTION: Lupus nephritis (LN) is an autoimmune glomerulonephritis secondary to systemic lupus erythematosus. Commonly, immunosuppressive agents are required for treating LN. However, frequent use of conventional immunosuppressants may produce a variety of side effects. Hence, seeking alternative drugs for treating LN is very important. This report aims to figure out the immunoregulatory efficacy of celastrol (CLT) in LN. MATERIAL AND METHODS: A spontaneous in vivo model of LN was established in FasL-deficient B6/gld mice. ELISA was used for analyzing serum creatinine (Scr) and anti-dsDNA levels in mice. IHC staining, immunofluorescence and hematoxylin-eosin and PAS staining were applied to determine renal immunopathology and histology. Cytokine gene levels were assessed using RT qPCR. CD4+Foxp3+ Treg frequency in murine kidneys, lymph nodes and spleens was determined using flow cytometry analysis. RESULTS: CLT treatment alleviated renal dysfunction and renal injury in LN-prone B6/gld mice. Moreover, CLT reduced CD3+ T cell infiltration and inhibited proinflammatory cytokine expression in renal tissues of B6/gld mice. Importantly, CLT enhanced CD4+FoxP3+ Treg frequency in kidneys, lymph nodes and spleens of B6/gld mice. CONCLUSIONS: CLT exerts therapeutic effects on murine LN by improving renal function and immunopathology and inducing CD4+FoxP3+ Tregs.