肝脏缺血再灌注(IR)损伤发生机制复杂，直接影响手术预后。巨噬细胞(mø)和调节性T细胞(Treg)在肝脏IR损伤和修复中扮演了重要角色。近期研究发现，Roquin-1和外泌体介导的信号传递发挥了重要的免疫调节作用。本组研究发现，肝脏IR抑制了Roquin-1，肝内mø数量先升后降，而Treg呈现相反的变化。干扰Roquin-1的表达加重了肝脏损伤。由此，提出本假说：Roquin-1通过抑制mø的炎性反应减轻了早期损伤，并通过促进Treg的抑炎性反应加快了损伤修复。通过外泌体调控mø/Treg相互作用是Roquin-1影响肝脏IR的重要机制。本课题计划利用Roquin-1san/san小鼠，建立IR模型和体外细胞共培养模型，研究Roquin-1是否通过外泌体调控mø/Treg的相互作用，及其对肝脏IR的影响。探索肝IR中mø/Treg相互作用机制，有助于为临床干预提供新的靶点和理论依据。

Liver ischemia reperfusion （IR） injury is a complex pathophysiological process resulting in significantly impaired postoperative recovery. The liver resident macrophage (mø) and regulatory T cell (Treg) plays an important role in liver IR. Recent studies have shown the critical roles of Roquin-1 and exosome in regulating immune response. Our group found that Roquin-1 was inhibited by hepatic IR. The numbers of mø increased first and then decreased, while opposite changes were found in Treg.Roquin-1 san/san aggravated liver IR injury. Thus, we hypothesize that Roquin-1 signaling may alleviated liver IR injury by inhibiting pro-inflammatory activation of mø at the early stage, and promote hepatic recovery by enhancing regulatory function of Treg at the late stage. The exosome mediated regulation of mø/Treg by Roquin-1 may be the essencial underlying mechanism. We plan to take advantage of Roquin-1 san/san mice to study the regulation of the crosstalk between mø and Treg by Roquin-1 signaling. The underlying mechanism will be analyzed as well by in vivo IR model and in vitro mø/Treg co-culture model. Studies on how Roquin-1 regulate the crosstalk of mø/Treg will not only help to illustrate the mechanism involved in liver IR, but also provide new target and related theory basis for therapy.