Study on the mechanism of Jieduquyuziyin prescription improving the condition of MRL/lpr mice by regulating T cell metabolic reprogramming through the AMPK/mTOR pathway

Abstract

Ethnopharmacological relevance

Systemic lupus erythematosus (SLE) is an autoimmune disease associated with T cell metabolic reprogramming. The traditional Chinese medicine Jieduquyuziyin prescription (JP) has demonstrated therapeutic efficacy in SLE, yet its mechanisms remain unclear. This study evaluates the therapeutic effects of JP on SLE, focusing on T cell metabolic reprogramming.

Aim of the study

To assess JP's therapeutic effects on SLE and its role in regulating T cell metabolism.

Materials and methods

MRL/lpr mice were treated with JP and assessed for spleen index, serum biochemistry, autoantibodies, urine protein levels, and histopathology. Th17 and Treg proportions were analyzed via flow cytometry. CD4⁺T cells were evaluated for the Th17/Treg transcription factors and glucose metabolism indicators through ELISA, quantitative real-time PCR, and assay kits. The AMPK/mTOR pathway was investigated using Compound C in vivo and in vitro.

Results

JP alleviated SLE symptoms, promoted Treg differentiation, and inhibited Th17 differentiation, restoring immune balance. JP reduced glycolysis-related metabolites and enzymes in CD4⁺T cells, including glucose, pyruvate, lactate, Glucose transporters1 (Glut1), Hexokinase2 (HK2), Pyruvate kinase isozyme typeM2 (PKM2), lactic dehydrogenase A (LDHA). JP decreased RORC expression, a key transcription factor for Th17 cells, and increased Foxp3 expression, a key regulator of Treg cells. JP activated AMPK and inhibited mTOR signaling in both mouse and Jurkat cell models.

Conclusions

JP alleviates SLE symptoms by modulating T cell metabolic reprogramming, primarily through inhibiting glycolysis and restoring the Th17/Treg balance via the AMPK/mTOR pathway. These findings underscore the significance of targeting metabolic pathways in the treatment of autoimmune diseases.