Hypoxia-inducible Factor-2? Is Necessary To Affect Regualr T Cell Cytotoxicity In Liver Ischemia-reperfusion Injur

Hepatic ischemia-reperfusion injury(ischemia-reperfusion injury,IRI)is a important clinical problem in liver transplantation,especially for donates from cardiac death(DCD),T cell immunity and Kupffer cell infiltration and release of inflammatory mediators are recognized as the primary mechanisms.In our previous studies,we found that HIF-2? knockout Fas ligand allows the outer circumferential surface of NKT cells upregulated can induce NKT cells to the ischemic kidney infiltration and aggravate renal ischemia-reperfusion injury.And HIF-2? play an important role in the inflammatory response.We hypothesized that the expression of HIF-2? also plays a role in the liver IRI.We used Lck-Cre transgenic mice to interfere HIF-2? gene in T cells and NKT cells,the mice were then performed with hepatic ischemia-reperfusion experiments.We found that HIF-2? knockout also increased hepatic ischemia-reperfusion injury.However,it is interesting that unlike spleen NKT cells' Fasl activation,the liver NKT cells FasL showed no significant activation.Through further research,we found that the number and function of regulatory T cells in the liver have a significant difference between knockout and unkonocked groups.Also,in unknockout group mice with the A2 A adenosine receptor agonist CGS21680 pretreatment befor liver IRI can find significantly reduced injury;however,CGS21680 pretreatment faired to reduce IRI of mice in knockout group.So Hif-2?is a vital factor determinating whether CGS21680 can function.After the liver regulatory T cells in wild-type mice extracted,first by CGS21680 treatment increased the proportion of cells in the liver regulatory T.And,Ras-MAP kinase pathway in Hif-2? / ARA on regulatory T cells plays an important role in regulating the function.In conclusion,our results not only once again proven results before and further revealed HIF-2? difference in mechanism of action of different organs.