树突状细胞（DC）是影响肾缺血再灌注损伤（IRI）的关键性免疫细胞之一。缺氧和缺氧诱导因子（HIF）-1α已被证实对DC功能有影响，HIF-2α则未见相关研究报道。我们在预实验中发现HIF-2α敲除导致DC自发性成熟，肾IRI明显加重，且不能被腺苷A2a受体（adora2a）激活剂缓解。我们推测DC中存在着HIF-2α对Adora2a的表达调控，HIF-2α因此影响特定DC亚群的功能进而改变肾IRI炎症反应的转归。我们设想获得DC特异性HIF-2α敲除或高表达小鼠，观察其DC表型和功能变化。对DC中HIF-2α/Adora2a调控关系进行研究确认并观察这种调控关系对肾IRI的影响。观察T/NKT细胞在上述研究体系中的作用。通过磁珠分选不同DC亚群过继输注无DC小鼠从而确定起关键作用的DC亚群。本研究将进一步揭示缺氧对DC功能的影响及其调控机制，并可能为肾IRI提供新的干预靶点。

Dendritic cell (DC) is among the key immune cells that influence renal ischemia-reperfusion injury (IRI). It has been reported that hypoxia and hypoxia-inducible factor-1 (HIF-1) play important roles in the maturation and function of DCs. However, the role of HIF-2 has not been documented before. In the preliminary studies employing Cd11cCre+HIF-2α-/- mice, we found that HIF-2α knockout led to much more severe renal IRI, which couldn’t be mitigated by CGS21680, an activator of adenosine A2a receptor (adora2a). We speculate that there is a regulatory relationship between HIF-2 and adora2a in DCs, which affect the function of specific DC subpopulations as well as the inflammatory process in renal IRI. We plan to produce DC-specific HIF-2α knockout and overexpression mice by Cre-Loxp system and based on these mice we can define the role of HIF-2α on the maturation, phenotype and function of DCs. The regulatory relationship between HIF-2 and adora2a in DCs will be determined by promoter studies. Mice genetically modified to overexpress HIF-2α but lack adora2a will help to further define the relationship between HIF-2 and adora2a in vivo. We also plan to employ HIF-2α and Rag1 double knockout mice to define the role of T/NKT cells in HIF-2α knockout-induced aggravated IRI. Adoptive transfer of WT or HIF-2α-deficient DC subpopulations into mice that have no DCs will help to find out the specific DC subpopulation that determines the outcome of renal IRI. This study may further disclose how hypoxia regulates the function of DCs, and also, may lead to new therapeutic protocols to alleviate renal IRI.