Therapeutic Effects of Triptolide on the Balance of Th17/Treg Cells via AKT/mTOR/p70S6k Signaling Pathway in Lupus-like Mice

Abstract T cell subsets play a critical role in immune regulation. T helper 17 (Th17) cells induce tissue inflammation and autoimmune response while regulatory T (Treg) cells mediate autoimmune tolerance and inhibit autoimmune response. Recent studies have shown that the important factors for the pathogenesis and disease activity of systemic lupus erythematosus (SLE), a chronic inflammatory autoimmune disease, are an increased number of Th17 cells and a decreased number or reduced functions of Treg cells. Triptolide is the main active ingredient of Tripterygium wilfordii Hook F (TWHF). It not only has anti-inflammatory, antiproliferative, immune modulation, and proapoptotic activity effects, but is also effective in treating SLE. However, the underlying mechanism of how triptolide works is still unclear. For the purpose of evaluating the impact of triptolide on the induction of Th17 and Treg cells, we conducted relevant experiments with respect to the number and activities of Th17 and Treg cells in vivo and in vitro . In vivo , intragastrically administered triptolide effectively ameliorated the clinical and histological symptoms in lupus-like mice, increased the number of induced Treg cells and reduced the number of Th17 cells in the spleen and their secretion. In vitro , triptolide is able to promote the differentiation of Treg cells and inhibit Th17 formation by inhibiting the AKT/mTOR/p70S6K pathway. Therefore, we posit that triptolide can help to deter the development of inflammation and ultimately treat SLE through regulation of the Th17 and Treg cells balance.