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

在西方国家，肝脏疾病正在增加，而且远远没有足够的器官捐赠者来治疗如此多的终末期肝病患者。慢性肝炎会导致疤痕形成(肝硬变)和肝功能衰竭，唯一有效的治疗方法是肝移植。淋巴细胞是白细胞的一种，是人体免疫系统的重要组成部分。它们通常与感染作斗争，但如果它们持续存在或变得不适当地激活，它们可能会导致肝脏损伤，作为慢性肝炎或炎症的一部分，从而导致疤痕和肝功能衰竭。淋巴细胞被称为趋化因子的分子引导到肝脏炎症部位，这些分子是对炎症做出反应而产生的。这些趋化因子是特殊的，因为它们可以引导特定的淋巴细胞组进入/重新聚集到特定的组织。这些群体包括破坏效应淋巴细胞和调节细胞，它们抑制炎症，导致损伤的消退。肝脏损伤的结果取决于这些炎症和抗炎调节淋巴细胞之间的平衡，而平衡又将取决于a)哪种类型的细胞从血液中被招募到肝脏b)肝脏内塑造特定淋巴细胞生存、激活和扩张的信号。将平衡转向抗炎调节细胞可以预防肝脏炎症并促进消退，从而逆转进展为纤维化/肝硬变。我们希望研究相关的分子信号，然后利用我们的知识开发新的治疗方法，使用抗炎调节性淋巴细胞作为细胞疗法来治疗慢性肝病。

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.