Dynamic Observation And Significance Of IL-17and IL-22in Acute Rejection After Rat Liver Transplantation

Research background：For many end-stage liver diseases, liver transplantationremains the best available treatment option. However, the acute rejection aftertransplantation is still the leading cause of early graft failure. For more than2decades, theTh1/Th2paradigm has been used to explain most of the phenomena related totransplantation immunity. In recent years, this paradigm has been updated following thediscovery of Th17, a newly Th cell lineage, which plays an important role in adaptiveimmune homeostasis by secretion of the proinflammatory cytokine, IL-17and IL-22.Research Objective and Theoretical significance: To discuss whether IL-17andIL-22are involved in the acute rejection of liver transplantation process, to preliminarilyunderstand the function of IL-17and IL-22in liver transplantation, and to provide newreference index for the monitoring of liver graft condition, we established the rejection andtolerance models in rats by detecting the dynamic change of IL-17and IL-22in serum andliver tissue.Method: We get the LEW rats with60and the BN rats with60in closed population.Experimental animals are divided into two groups: LEW-to-BN rats group are rejectiongroup(n=30), while BN-to-LEW rats group be the tolerance one(n=30). The modified livertransplantation is used to build the model. Getting the blood from the abdominal aorta andgetting the liver tissue on day1、 day3、 day5、 day7post transplantation andpre-transplantation respectively. The serum IL-17level in the transplantation model ismeasured by ELISA，while immunohistochemistry, Western blot, and RT-PCR are used todetect the IL-17and IL-22dynamic changes of cell level, protein level and mRNA level inliver.Result: In the rejection group,the serum of IL-17level are higher than that in thetolerance group in the day1、day3、day5、day7(t=-14.5、-19.6、-17.4、-13.4P<0.05). Inliver tissue, the upregulation of IL-17for rejection group, including the frequencies of positive lymphocytes, protein level and mRNA level, significantly detected compared totolerance group in the day3、day5、day7; similarly in liver tissue, the upregulation of IL-22for rejection group, including the frequencies of positive lymphocytes, protein level andmRNA level, also significantly detected compared to tolerance group in the day1、day3、day5; meanwhile the amount of STAT3mRNA of rejection group increased in liver in theday3、day5、day7compared to tolerance group.Conclusion: The results suggest that the level of IL-17is raised in acute rejection ofrat liver transplantation, and is positive correlated with its pathological class; the secretionof IL-22and STAT3increase in acute rejection of rat liver transplantation；IL-17and IL-22are related to the development of graft rejection after liver transplantation due to STAT3activation; detecting the dynamic change of IL-17and IL-22can be a new target indiagnosis of acute rejection after liver transplantation in clinical.