Th17 promotes acute rejection following liver transplantation in rats

T help cell 17 (Th17), recently identified as a new subset of CD4(+) T cells, has been implicated in autoimmune diseases, tumor immunity, and transplant rejection. To investigate the role of Th17 in acute hepatic rejection, a rat model of allogeneic liver transplantation (Dark Agouti (DA) to Brown Norway (BN)) was established and isogeneic liver transplantation (BN to BN) was used as controls in the study. The expression of Th17-related cytokines in the liver and peripheral blood was determined by immunohistochemistry, flow cytometry, enzyme-linked immunosorbent assay (ELISA), or real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Strong expression of interleukin-17A (IL-17A), IL-6, transforming growth factor-β (TGF-β), IL-8, and myeloperoxidase (MPO) was observed in liver allografts. The ratios of Th17 to CD4(+) lymphocytes in the liver and peripheral blood were dramatically increased in the allograft group compared with the control (P<0.01). Secreted IL-17 and IL-6 in liver homogenate and serum were significantly elevated in the allograft group, while secreted TGF-β was increased in liver homogenate and decreased in serum compared with the control (P<0.01). The messenger RNA (mRNA) levels of IL-17, IL-21, and IL-23 were enhanced in the allografts compared with the control (P<0.01). Correlation analysis showed significant correlations between IL-17 and IL-6 and TGF-β and between IL-17 and IL-21 and IL-23. The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.