IL-17 promotes Type 1 T cell response through modulating dendritic cell function in acute allograft rejection

• CD3 + T cell produces high IL-17 during early allograft rejection.
• Blockage of IL-17 activity inhibits DC maturation and type 1 immune response.
• Adoptive transfer with anti-IL17 treated DC ameliorates allograft rejection.
• IL-17-treated BMDCs show an increased capacity to enhance T cell function.

IL-17 is a cytokine that produced by various type of cell. Previous studies have been shown that IL-17 plays a critical role in the pathogenesis of different diseases. However, few studies have addressed the source and mechanism of IL-17 in the development of allograft rejection response. In this study, we present that the IL-17 expression reaches the strongest response at the early stage of cardiac allograft rejection, and was elevated earlier than DC maturation. The IL-17 is predominantly produced by CD3+ T cells, whereas CD11c, CD11b, and NK1.1 positive cells rarely expressed IL-17. It is worth noting that blockade of endogenous IL-17 activity suppressed DC maturation, decreased inflammatory cytokines and impaired Th1 immune response during acute allograft rejection. Furthermore, adoptive transfer with DCs from IL-17-treated mice had a significant longer allograft survival time and decreased number of IFN-γ produced by T cells. Consistently, in an in vitro experiment, recombinant IL-17 significantly up-regulate co-stimulatory molecules of bone marrow derived dendritic cells (BMDCs), and IL-17-treated BMDCs show that an increased capacity to enhance T cell function was also observed. In conclusion, our data provide clear evidence that the early elevated level of IL-17 contributes to allograft rejection through modulating dendritic cell function.