Intrahepatic signals involved in the recruitment and differentiation of IL-17 secreting T cells and Regulatory T cells i

肝内信号参与分泌 IL-17 的 T 细胞和调节性 T 细胞的招募和分化

• 批准号: G1002552/1
• 负责人: Ye Oo
• 金额: $ 149.7万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G1002552%2F1
• 关键词: Intrahepatic; signals; involved; recruitment; differentiation

Liver disease is increasing in Western countries and there are nowhere near enough organ donors to treat the number of patients with end-stage liver disease. Chronic hepatitis leads to scarring (cirrhosis) and liver failure and the only effective treatment is liver transplantation. Lymphocytes are a type of white blood cell and an important part of the body‘s immune system. They normally fight infections but if they persist or become inappropriately activated they can cause liver injury as part of chronic hepatitis or inflammation that leads to scarring and liver failure. Lymphocytes are directed to sites of liver inflammation by molecules called chemokines that are produced in response to inflammation. These chemokines are specific in that they can direct the entry/ recruitment of particular groups of lymphocytes to specific tissues. These groups include damaging effector lymphocytes and regulatory cells which damp down inflammation leading to resolution of damage. The outcome of liver injury depends on the balance between these inflammatory and anti-inflammatory regulatory lymphocytes which in turn will be determined by a) which types of cells are recruited to the liver from blood b) signals within the liver that shape the survival, activation and expansion of specific lymphocytes. Shifting the balance towards anti-inflammatory regulatory cells may prevent liver inflammation and promote resolution thereby reversing progression to fibrosis/cirrhosis. We would like to investigate the molecular signals involved and then exploit our knowledge to develop novel therapeutic approaches using anti-inflammatory regulatory lymphocytes as cell therapy to treat chronic liver diseases.

肝病在西方国家正在增加，而且没有足够的器官捐赠者来治疗终末期肝病患者的数量。慢性肝炎会导致疤痕（肝硬化）和肝功能衰竭，唯一有效的治疗方法是肝移植。淋巴细胞是一种白色血细胞，是人体免疫系统的重要组成部分。它们通常对抗感染，但如果它们持续存在或被不适当地激活，它们可能会导致肝损伤，作为慢性肝炎或炎症的一部分，导致疤痕和肝功能衰竭。淋巴细胞被称为趋化因子的分子导向肝脏炎症部位，趋化因子是对炎症的反应。这些趋化因子是特异性的，因为它们可以指导特定淋巴细胞群进入/募集到特定组织。这些组包括破坏性效应淋巴细胞和调节细胞，它们抑制炎症，导致损伤的解决。肝损伤的结果取决于这些炎性和抗炎性调节淋巴细胞之间的平衡，这反过来将由a）哪些类型的细胞从血液中募集到肝脏B）肝脏内的信号决定，所述信号形成特定淋巴细胞的存活、活化和扩增。将平衡向抗炎调节细胞转移可以预防肝脏炎症并促进消退，从而逆转纤维化/肝硬化的进展。我们希望研究所涉及的分子信号，然后利用我们的知识开发新的治疗方法，使用抗炎调节淋巴细胞作为细胞疗法来治疗慢性肝病。