权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

In vivo imaging reveals inflammatory and immune processes of adipose tissue obesity.

体内成像揭示脂肪组织肥胖的炎症和免疫过程。

基本信息

批准号：
21790865
负责人：
NISHIMURA Satoshi
金额：
$ 2.75万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2009
资助国家：
日本
起止时间：
2009 至 2010
项目状态：
已结题

项目摘要

Metabolic syndrome is a major risk factor of cardiovascular events, and obese visceral adipose tissue remodeling and malfunctioning based on chronic inflammation and local immunological changes plays a central role. To assess dynamic interplay between multiple cell-types in obese adipose, a visualization technique in vivo was therefore developed. In vivo imaging revealed close spatial and temporal interrelationships between angiogenesis and adipogenesis in obese adipose, and these inflammatory cell clusters included inflammatory "M1" macrophages). Increased leukocyte-platelet-endothelial cell interactions in the microcirculation of obese adipose were also observed, a hallmark of inflammation. The activation of platelet and increased adhesion molecule contribute to the inflammatory cellular dynamics, such as "rolling and adhesion" of leukocyte and platelet. We also found that large numbers of CD8+ effector T cells infiltrated into obese adipose. The infiltration by CD8+ T cells preceded the accumulation of macrophages, and immunological and genetic depletion of CD8+ T cells reduced macrophage infiltration and adipose tissue inflammation, and ameliorated systemic insulin resistance. CD8+ T cells contribute to the macrophage recruitment in obese adipose tissue, and adipose tissues inflammation in obesity. This imaging technique can be applied to many diseases including thrombosis. Our results clearly demonstrated the power of our imaging technique to analyze complex cellular interplays in vivo and to evaluate new therapeutic interventions against them.

代谢综合征是心血管事件的主要危险因素，而基于慢性炎症和局部免疫改变的肥胖内脏脂肪组织重塑和功能障碍起着核心作用。为了评估肥胖脂肪中多种细胞类型之间的动态相互作用，因此开发了一种体内可视化技术。体内成像显示肥胖脂肪中血管生成和脂肪生成在空间和时间上密切相关，这些炎症细胞团包括炎性“M1”巨噬细胞)。肥胖脂肪微循环中白细胞-血小板-内皮细胞相互作用增加，这是炎症的标志。血小板的活化和黏附分子的增加有助于炎症细胞动力学，如白细胞和血小板的“滚动和黏附”。我们还发现大量CD8+效应T细胞浸润到肥胖脂肪中。CD8+ T细胞的浸润先于巨噬细胞的积累，CD8+ T细胞的免疫和遗传耗竭减少巨噬细胞浸润和脂肪组织炎症，并改善全身胰岛素抵抗。CD8+ T细胞参与肥胖脂肪组织巨噬细胞募集和肥胖脂肪组织炎症。这种成像技术可以应用于包括血栓在内的许多疾病。我们的结果清楚地证明了我们的成像技术在分析体内复杂的细胞相互作用和评估针对它们的新治疗干预方面的能力。