Shen-Yi, A Chinese Herbal Formula, Modulates Th1/Th2 Balance In Murine Lupus Nephrititis: Effects On Renal And Splenic Microenvironment

CD4+ T helper cells, which upon activation differentiate into two defined subsets, TH1 and TH2, differing in their capacities of cytokine production with distinct immunopathological consequences, have been considered to be in the majority in the inflammatory cells infiltrating into kidney of MRL/lpr lupus-prone mice. Our analysis revealed that the progression of lupus nephrititis (LN) in MRL/lpr mice was correlated with an enhanced expression of interleukin-4 (IL-4, a Th2 type cytokine) vs interferon-gamma (IFN-r, a Thl type cytokine) positive stained cells, in parallel with an aggravated renal pathological changes, implying an imbalance towards Th2 predominance in MRL/lpr mice. Shen-Yi, a Chinese herbal formula, was potential in modulating Thl/Th2 balance resulting in therapeutic effects on survival rate, proteinuria, and renal pathological changes. Using flowcytometric and gene chip methods, we identified the effects of Shen-Yi on spleen and microenvironment within renal tissue, which contribute to differentiation of T helper cells. Regarding Thl/Th2 in spleen, it was found that upon PHA-P stimulation, the extent of expansion of Th2 cells and the ratio of Th2 to Thl in treatment group were both lower than those in control one. Further, CD4+ T helper cells were sorted using FACScan Sorting System and RT-PCR semiquantative method showed a reduction in the ratio of IL-4/ IFN- y mRNA in treatment group compared to it in control one. According to the results of mice 8192 genes microarray, Shen-Yiinitiated an obvious expression change of 279 genes, among which Th2 type cytokine inducing factors, such as IL-18 binding protein (IL-18BP) and CD28, were down regulated greatly compared to control mice, suggesting a underlying mechanism of this Chinese herbal formula in shifting Thl/Th2 balance in kidney. These results indicate that Shen-Yi can modulate the Th2 predominance in MRL/lpr mice, which might related to regulation on differentiation orientation of T helper cells within spleen and the remodeling effects on local renal microenvironment.