Jieduquyuziyin prescription regulates the differentiation of Tfh cells in systemic lupus erythematosus through lysophosphatidyl ethanolamine metabolism.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: The formula of Chinese herbal compound Jieduquyuziyin prescription (JP) can be used to treat systemic lupus erythematosus (SLE) and Its efficacy has been confirmed by clinical studies and has been approved for clinical treatment in China hospitals. The therapeutic mechanism of JP still needs further study, and this study focuses on its role in T cell differentiation and lipid metabolism regulation. AIM OF THE STUDY: To clarify the effects of JP on Tfh cell differentiation and explore the role of lysophosphatidyl ethanolamine (LPE) metabolic pathway in it. METHODS: The chemical composition of JP decoction was analyzed by high performance liquid chromatography combined with mass spectrometry (HPLC-MS). MRL/lpr mice served as the SLE model. The therapeutic effect of JP on SLE and the inhibitory effect on T cell subsets were evaluated by histoopathology, immunofluorescence, flow cytometry analysis and enzyme-linked immunosorbent assay (ELISA). Meanwhile, lipid metabolomics and transcriptomics were combined to explore the potential molecules by which JP regulates Tfh cells through the LPE metabolic pathway, and were verified by primary cell polarization experiments in vitro. Finally, molecular docking was performed to identify the active components of JP and validate the binding stability between these components and the key target. RESULTS: JP significantly alleviated kidney damage, reduced expression of autoantibodies and inflammatory factors, reduced the proportion of Tfh cells, and regulated the glycerol phospholipid metabolic pathway in SLE model mice. The proportion of Tfh cells was significantly correlated with the metabolism of LPE metabolites, and pla2g2f was a potential molecule that JP regulated LPE metabolism and affected Tfh cells. Cell experiments confirmed that JP downregulates pla2g2f expression and suppresses Tfh cell polarization in vitro. Molecular docking showed stable binding of JP active components (Cafestol, Daidzein, Isoliquiritigenin, Rifampicin, and Neochlorogenic acid) to PLA2G2F. CONCLUSION: JP can inhibit pla2g2f that involved in LPE metabolism to regulate the differentiation of Tfh cells and alleviate SLE disease. These findings provide a new perspective on the immune metabolic regulation of JP.