CHINESE HERBAL MEDICINE AND PREDNISONE INCREASE PROPORTION OF SPLENIC CD4+CD25-FOXP3+ CELLS AND ALLEVIATE GLOMERULAR LESION IN MRL/LPR MICE

Objective: This study investigated the effects of Chinese herbal medicine and prednisone on CD4+FoxP3+ T cells (Tregs) and Th17 cells in the MRL/lpr mouse model of systemic lupus erythematosus.
Methods: MRL/lpr mice were treated with herbal medicine (yin-nourishing and heat-clearing therapy), prednisone, and a combination of both for 7 weeks. The proportions of CD4⁺CD25⁺FoxP3⁺ cells, CD4⁺CD25^-FoxP3⁺ cells, and CD4⁺IL-17⁺ cells in splenic mononuclear cell suspension were determined by flow cytometry. Histological slices of kidneys were stained by H&E, PAS, and Masson’s method. Activity indexes (AI) of glomerular lesions were scored.
Results: The result showed that both herbal medicine and prednisone significantly increased the proportion of CD4⁺CD25^-FoxP3⁺ cells (P<0.05), but lowered the proportion of CD4⁺CD25⁺FoxP3⁺ cells (P<0.05) and CD4⁺IL-17⁺ cells (P<0.05) in MRL/lpr mice. Consequently, CD4⁺CD25^-FoxP3⁺ cells became dominant CD4⁺ FoxP3⁺ cells after either treatment. AIl the glomerular lesions in both herbal medicine group and prednisone group were significantly lower than those in the model group (P<0.05). AI was positively related with the proportion of CD4⁺IL-17+ cells (Spearman's rho= 0.4958, P＜0.05), but was negatively correlated with the proportions of CD4⁺Foxp3⁺ cells(Spearman's rho= -0.5934，P＜0.05) and CD4⁺CD25^-FoxP3⁺ cells (Spearman's rho= -0.5914，P＜0.05).
Conclusion: Both Chinese herbal medicine and prednisone significantly enhanced the proportion of CD4⁺CD25^-FoxP3⁺ cells and reduced the proportion of Th17 cells in lupus-prone MRL/lpr mice. Increased proportion of CD4⁺CD25^-FoxP3⁺ cells was correlated with less severe glomerular lesions, indicating that CD4⁺CD25^-FoxP3⁺ cells might play a regulatory role in the treatment of systemic lupus erythematosus.

Keywords
Systemic lupus erythematosus; regulatory T cells; Herbal medicine; Prednisone