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Xinghui Song1, Jinglin Gao1, Huicong Liu1
1Department of Rheumatology, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545027, China.
Abstract:
This study aimed to explore the therapeutic effect and mechanism of rapamycin (RAPA) on systemic lupus erythematosus (SLE) in BALB/C mice induced by pristane. The mice were randomly divided into 5 groups (n = 6): control, model, saline, RAPA (1 mg/kg) and RAPA (2 mg/kg). All groups were injected with pristane except control. HE staining revealed 1 mg/kg and 2 mg/kg RAPA treatments obviously alleviated pathological changes in the kidney of SLE mice such as glomeruli enlargement, hyperplasia of mesangial cells, epithelial and endothelial cells, infiltration of inflammatory cells, and edema-like degeneration of renal tubules. Compared with control group, body weights and anti-ribosomal P-protein antibody (ARPA) level of the mice in model group and saline group decreased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody and urine protein in model group and saline group increased (P < 0.05). However, compared with model group and saline group, body weights of the mice in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group increased (P < 0.05), while immune complex deposition and levels of anti-dsDNA antibody, anti-smRNP antibody, ARPA, and urine protein in RAPA (1 mg/kg) group and RAPA (2 mg/kg) group decreased (P < 0.05). Compared with control group, the proportion of dentritic cells (DC) in the kidney and peripheral blood decreased while the proportion of Th1, Th2 and Th17 cells in the spleen, kidney and peripheral blood increased in model group and saline group (P < 0.05). Compared with model group and saline group, 1 mg/kg and 2 mg/kg RAPA treatments boosted the proportion of DC in the kidney and peripheral blood, reduced the proportion of Th1 and Th17 cells in the spleen, kidney and peripheral blood, and lessened the proportion of Th2 cells in the kidney and peripheral blood (P < 0.05). In conclusion, RAPA alleviated renal damage in SLE mice through improving immune response and function.
Insights
Rapamycin (RAPA) treatment significantly alleviates kidney damage in mice with systemic lupus erythematosus (SLE). RAPA improves immune responses by modulating dendritic cells and T helper cells, offering a potential therapeutic strategy for SLE.
Area of Science:
- Immunology
- Nephrology
- Pharmacology
Background:
- Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread inflammation and organ damage.
- Pristane-induced lupus in BALB/C mice serves as a relevant model for studying SLE pathogenesis and evaluating therapeutic interventions.
- Understanding the immunomodulatory mechanisms of drugs like rapamycin is crucial for developing effective SLE treatments.
Purpose of the Study:
- To investigate the therapeutic effects of rapamycin (RAPA) on kidney damage in a mouse model of systemic lupus erythematosus (SLE).
- To elucidate the underlying immunomodulatory mechanisms by which RAPA exerts its therapeutic effects in SLE.
- To evaluate the impact of RAPA on specific immune cell populations and autoantibody production in SLE.
Main Methods:
- BALB/C mice were induced with pristane to establish an SLE model and randomly assigned to control, model, saline, and two RAPA treatment groups (1 mg/kg and 2 mg/kg).
- Histopathological examination (HE staining) of kidney tissues was performed to assess pathological changes.
- Levels of autoantibodies (anti-dsDNA, anti-smRNP, ARPA), urine protein, and immune complex deposition were measured.
- Flow cytometry was used to analyze the proportions of dendritic cells (DC), Th1, Th2, and Th17 cells in the spleen, kidney, and peripheral blood.
Main Results:
- Rapamycin treatment significantly alleviated kidney pathological changes, including glomeruli enlargement and inflammatory cell infiltration.
- RAPA administration led to increased body weight and decreased levels of immune complex deposition, anti-dsDNA, anti-smRNP, and urine protein compared to the model group.
- RAPA modulated immune cell populations by increasing dendritic cell proportions and decreasing Th1, Th2, and Th17 cell proportions in the spleen and kidneys.
Conclusions:
- Rapamycin effectively alleviates renal damage in a mouse model of SLE.
- The therapeutic effects of RAPA in SLE are associated with the improvement of immune response and function, including modulation of dendritic cells and T helper cells.
- Rapamycin demonstrates potential as a therapeutic agent for managing systemic lupus erythematosus, particularly its renal manifestations.
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