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

调节性 T 细胞募集至发炎肝脏的分子基础

• 批准号: G0501638/1
• 负责人: Ye Oo
• 金额: $ 25.74万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0501638%2F1
• 关键词: molecular; basis; regulatory; cell; recruitment

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.

机体的免疫系统在识别自身抗原的同时，也识别并攻击入侵的非自身抗原。大多数慢性肝病是由于从血液中招募称为 T 细胞的白细胞而发生的，这些白细胞旨在抵抗感染，但副作用也会导致组织损伤。近年来，T 细胞的一个子集被称为调节细胞 (Treg)，它可以抑制其他 T 细胞引起的组织损伤。这些细胞的进化是为了防止感染免疫反应过程中的附带损害，但最近的证据表明它们在慢性炎症、移植排斥、自身免疫性疾病和肿瘤免疫反应中很重要。与此相一致的是，我在慢性炎症性肝病患者中检测到 Treg 数量增加。我假设特定的 Treg 在炎症过程中会被招募到肝脏，并且特定的分子将控制这个过程。我计划使用组合方法来检验这一假设，其中在体外人体系统中以及通过体内转移细胞来研究这些细胞的归巢行为。这些研究将是首批研究 Treg 如何从血液中募集到肝脏炎症部位的研究之一，并可能为炎症性肝病提出新的治疗方法，其中控制组织内局部 Treg 的数量有利于炎症的消退。