Role of iNKT cells and the lymphoid structures within visceral adipose tissue in the control of inflammation and obesity

在大多数工业化国家，肥胖已经成为一个主要的健康问题。它易患心血管疾病，并与过早死亡有关。脂肪组织的慢性炎症在肥胖中很重要，但抗炎疗法的使用在恢复代谢健康方面的效果非常有限或没有效果。最近的研究表明，刺激脂肪组织中的某些免疫细胞群可以改善炎症，诱导体重减轻，并改善2型糖尿病。但其中涉及的确切机制仍不清楚。其中一个脂肪库，即大网膜，特别富含免疫团，在感染和腹膜炎(腹腔炎)期间，炎性细胞集中在这些免疫团中。在这个项目中，我们想要了解大网膜在调节炎症和肥胖发展中的作用。特别是，我们希望阐明这个器官是否对免疫干预在肥胖中的有益效果负责。我们将使用腹膜炎的小鼠模型来研究大网膜在炎症中的作用。这项工作将增进我们对炎症和腹膜腔防御感染的潜在机制的了解，并为开发治疗肥胖症炎症的治疗工具开辟新的道路。利用肥胖的小鼠模型，我们将研究大网膜在肥胖的发生发展中的作用以及通过免疫干预进行治疗。这项工作将为未来的翻译研究铺平道路，该研究着眼于人类的大网膜，以及它们在炎症环境(如阑尾炎和胰腺炎)和肥胖症中的靶向治疗益处。

Obesity has become a major health issue in most industrialised countries. It predisposes to cardiovascular disease and is associated with premature mortality. Chronic inflammation in adipose tissue is important in obesity, but use of anti-inflammatory therapies has had very modest or no efficacy in restoring metabolic health. Recent studies showed that stimulations of certain populations of immune cells in adipose tissue could improve inflammation, induce weight loss and ameliorate type 2 diabetes. But the precise mechanisms involved remain unknown. One fat depot, the omentum, is particularly rich in immune clusters where inflammatory cells are concentrating during infection and peritonitis (inflammation of the peritoneal cavity). In this project, we want to understand the role of the omentum in the regulation of inflammation and the development of obesity. In particular we wish to elucidate whether this organ is responsible for the beneficial effect of immune-intervention in obesity. We will use a mouse model of peritonitis to study the role of the omentum in inflammation. This work will enhance our knowledge concerning the mechanisms underlying inflammation and the defense of the peritoneal cavity against infections and open new roads for the development of therapeutics tools in the treatment of inflammation in obesity. Using a mouse model of obesity we will examine the role of the omentum in the development of obesity and its treatment by immune-intervention. This work will pave the way to future translational studies looking at the omentum in humans and the therapeutic benefit of their targeting in inflammatory settings (such as appendicitis and pancreatitis) and in obesity.