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-βwas 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-βand between IL-17 and IL-21 and IL-23.The present study demonstrates that Th17 plays a role in promoting rat liver allograft rejection.