JAML-CAR regulation of adipose tissue homeostasis

肥胖和与肥胖有关的疾病在全球处于流行病水平（世卫组织）。肥胖相关的炎症最近受到了广泛关注，因为它会给许多COVID-19患者带来毁灭性的后果。肥胖中慢性炎症的低水平导致了肥胖作为一种由代谢稳态紊乱引起的炎症性疾病的最新分类。脂肪组织中免疫细胞和代谢调节细胞（如脂肪细胞）之间的串扰调节脂肪组织的稳态。细胞内在和环境的变化会导致压力和细胞因子产生的改变，从而导致炎症反应，从而导致代谢下降和肥胖的发展。脂肪组织含有组织驻留免疫细胞群，包括γδ T细胞，在激活时产生大量的IL-17A和TNF-α。IL-17在调节体重、脂肪细胞分化和胰岛素和葡萄糖稳态中发挥作用。与食物摄入量相似的野生型小鼠相比，缺乏JAML蛋白的小鼠随着年龄的增长变得明显肥胖。JAML蛋白是组织内γδ T细胞的共刺激蛋白。我们假设JAML-CAR相互作用在调节γδ T细胞功能以维持脂肪组织稳态中起关键作用。我们计划通过观察γδ T细胞在肥胖发展过程中对脂肪细胞分化和体内平衡的直接控制来研究这些小鼠肥胖发展的机制。

Obesity and obesity-related diseases are at epidemic levels globally (WHO). Obesity-associated inflammation has recently received much attention due to its devastating consequences for many patients suffering from COVID-19. The low levels of chronic inflammation in obesity have led to the updated classification of obesity as an inflammatory disease that results from disturbed metabolic homeostasis. Crosstalk among immune cells and metabolic regulatory cells, such as adipocytes, in the adipose tissue regulate adipose tissue homeostasis. Cell intrinsic and environmental changes can lead to stress and alterations in cytokine production driving an inflammatory response that builds to metabolic decline and development of obesity. Adipose tissue contains populations of tissue-resident immune cells including γδ T cells that produce significant amounts of IL-17A and TNF-α when activated. IL-17 plays roles in regulation of body weight, adipocyte differentiation and insulin and glucose homeostasis. Mice deficient in the JAML protein that is costimulatory for tissue-resident γδ T cells become significantly obese with age compared to wildtype mice with similar food intake. We hypothesize that JAML-CAR interactions play a critical role in regulation of γδ T cell functions to maintain adipose tissue homeostasis. We plan to investigate the mechanism for development of obesity in these mice by looking at direct control of adipocyte differentiation and homeostasis by γδ T cells during development of obesity.