Toll-like receptor 2 deficiency promotes the generation of alloreactive Th17 cells after cardiac transplantation in mice.

• Alloreactive Th17 cells play an important role at the early stage of allograft rejection. • TLR2 deficiency enhances cardiac transplantation rejection in mice. • TLR2-deficient recipient mice show high alloreactive Th17 cells. • IL-6 secreted by dendritic cells of TLR2-deficient mice contributes to driving Th17 skewing. The emergence of alloreactive Th17 cells that mediate allograft rejection has provided an impetus to understand the factors affecting the generation of Th17 cells in allograft transplantation. How toll-like receptor 2 (TLR2) signalling regulates the generation of Th17 cells upon alloantigen stimuli remains unclear. In this study, we used a mouse model of cardiac allograft transplantation to investigate whether TLR2 signalling influences the development of Th17 cells. Here, we demonstrate that the TLR2-deficient recipient mice show high Th17 cells, both in spleens and allografts, as well as higher infiltrating inflammatory leukocytes in cardiac allografts compared to wild-type control recipient mice. mRNA expression of IL-17, IL-6, TNF-α, CCR6 and CCL20 within the allografts is markedly increased in TLR2-deficient recipient mice compared to wild-type recipient mice. In addition, TLR2 deficiency leads to upregulation of Signal transducer and activator of transcription 3 (STAT3) phosphorylation in both spleens and allografts. In an in vitro experiment, a mixed lymphocyte reaction was assessed, which further confirmed that TLR2 deficiency leads to a significant increase in the generation of Th17 cells compared with wild-type controls. Furthermore, IL-6 secreted by the dendritic cells of TLR2-deficient mice contributes to driving the generation of these Th17 cells. These results suggest that TLR2 signalling is important in regulating the development of Th17 cells after cardiac allograft transplantation. [ABSTRACT FROM AUTHOR]