A Gamma-Secretase Inhibitor (Dapt) Alleviates The Inflammation Of Paraquat-Induced Ali Mice By Regulating The Differentiation Of Th17 Cells

The Notch signaling pathway is critically involved in the proliferation and differentiation of T cells, key players in the pathogenesis of the inflammatory diseases. It was reported that Notch signaling can induce the differentiation of T helper 17 (Th17) cells and promote the expansion of interleukin-17 (IL-17). gamma-Secretase inhibitors (DAPT) have been used to effectively block Notch signaling and directly regulate Th17 responses through a Notch signaling-dependent pathway. The aim of this study was to determine whether a gamma-secretase inhibitor (DAPT) inhibits the differentiation of Th17 cells in mice with paraquat (PQ)-induced acute lung injury (ALI). DAPT ameliorated the inflammatory reaction of PQ-induced ALI. DAPT also significantly regulated Th17 cell responses and reduced the levels of IL-17A. These results suggested that DAPT could inhibit the differentiation of Th17 cells in mice with PQ-induced ALI. Thus, DAPT plays critical role in attenuating PQ-induced ALI and should be considered as a potential therapeutic agent.