The molecular basis of regulatory T cell recruitment to the inflamed liver

机体免疫系统识别和攻击入侵的非自身抗原，同时识别自身抗原。大多数慢性肝病的发生是由于血液中被称为T细胞的白细胞招募的结果，这种细胞旨在对抗感染，但作为副作用也会导致组织损伤。近年来，一种称为调节性细胞(Treg)的T细胞亚群已经被描述，它可以抑制由其他T细胞引起的组织损伤。这些细胞的进化是为了在对感染的免疫反应中防止附带损害，但最近的证据表明，它们在慢性炎症、移植排斥反应、自身免疫性疾病和肿瘤免疫反应中非常重要。与此一致，我在慢性炎症性肝病患者中检测到Treg的数量增加。我假设，在炎症过程中，特定的Treg将被招募到肝脏，并且特定的分子将控制这一过程。我计划使用一种组合的方法来检验这一假设，在这种方法中，这些细胞的归巢行为是在体外人体系统中研究的，也是通过在体内转移细胞来研究的。这些研究将是第一批研究Treg是如何从血液中招募到肝脏炎症部位的研究之一，并可能提出治疗炎症性肝病的新疗法，即操纵组织中局部Treg的数量，以利于炎症的消退。

Immune system of body recognise and attack invading non-self antigen at the same time recongnize the self antigen. Most chronic liver diseases occur as a consequence of the recruitment from blood of white blood cells called T cells which are designed to fight infection but as a side-effect also cause tissue damage. In recent years a subset of T cells called regulatory cells (Treg) has been described which suppresses tissue damage caused by other T cells. These cells evolved to prevent collateral damage during immune responses to infections but recent evidence suggests they are important in chronic inflammation, transplant rejection, autoimmune diseases and tumor immune response. Consistent with this, I have detected increased numbers of Treg in patients with chronic inflammatory liver diseases. I hypothesise that particular Treg will be recruited to the liver during inflammation and that specific molecules will control this process. I plan to test this hypothesis using a combined approach in which the homing behaviour of these cells in studied in human systems in vitro as well as by transferring cells in vivo. These studies will be among the first to investigate how Treg are recruited form the blood into sites of liver inflammation and may suggest new treatments for inflammatory liver diseases in which the number of local Treg within the tissue is manipulated in favour of resolution of inflammation.