CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity
CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity
复制标题
DOI：
10.1038/nm.1964
复制
发表时间：
2009-08-01
期刊：
影响因子：
82.9
通讯作者：
Nagai, Ryozo
中科院分区：
文献类型：
--
作者：
Nishimura, Satoshi;Manabe, Ichiro;Nagai, Ryozo
炎症越来越被认为是肥胖者代谢性疾病的一个关键过程。特别是，肥胖的脂肪组织表现出活跃的局部炎症特征。然而，目前人们对构成炎症级联反应的一系列事件或炎症发展的机制知之甚少。我们发现，在高脂饮食的小鼠，大量的CD8(+)效应T细胞渗入肥胖的附睾腺脂肪组织，而CD4(+)辅助T细胞和调节性T细胞的数量减少。CD8(+)T细胞的浸润先于巨噬细胞的聚集，CD8(+)T细胞的免疫和遗传缺失降低了巨噬细胞的浸润和脂肪组织的炎症，改善了全身性胰岛素抵抗。相反，过继地将CD8(+)T细胞转移到CD8缺陷小鼠会加重脂肪炎症。共培养和其他体外实验揭示了CD8(+)T细胞、巨噬细胞和脂肪组织之间相互作用的恶性循环。我们的发现表明，肥胖脂肪组织激活CD8(+)T细胞，进而促进巨噬细胞在该组织中的募集和激活。这些结果支持CD8(+)T细胞在脂肪炎症的启动和增殖中起重要作用的观点。
Inflammation is increasingly regarded as a key process underlying metabolic diseases in obese individuals. In particular, obese adipose tissue shows features characteristic of active local inflammation. At present, however, little is known about the sequence of events that comprises the inflammatory cascade or the mechanism by which inflammation develops. We found that large numbers of CD8(+) effector T cells infiltrated obese epididymal adipose tissue in mice fed a high-fat diet, whereas the numbers of CD4(+) helper and regulatory T cells were diminished. The infiltration by CD8(+) T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8(+) T cells lowered macrophage infiltration and adipose tissue inflammation and ameliorated systemic insulin resistance. Conversely, adoptive transfer of CD8(+) T cells to CD8-deficient mice aggravated adipose inflammation. Coculture and other in vitro experiments revealed a vicious cycle of interactions between CD8(+) T cells, macrophages and adipose tissue. Our findings suggest that obese adipose tissue activates CD8(+) T cells, which, in turn, promote the recruitment and activation of macrophages in this tissue. These results support the notion that CD8(+) T cells have an essential role in the initiation and propagation of adipose inflammation.