作者：刘纯来源：生物谷2012-5-17 14:09:57
05月16日，Nature在线发表了哈佛医学院微生物与免疫学系等机构的一篇题为PPAR-γ is a major driver of the accumulation and
phenotype of adipose tissue Treg cells 的研究论文，揭示了噻唑烷二酮药物作用疾病的细胞机制，并证明了具有独特功能的调节性T细胞的独立类群能精确地用于治疗疾病。
在过去的几十年来，肥胖和Ⅱ型
糖尿病同步急剧增加。这两种代谢紊乱症的一个最主要联系是同属于慢性低级炎症。持续的营养过剩促使内脏脂肪组织内白细胞的累积和激活，并延伸到其他组织，最终导致胰岛素抵抗、Ⅱ型
糖尿病和脂肪肝等代谢异常疾病。
虽然促炎症巨噬细胞入侵内脏脂肪组织被认为是驱动脂肪组织炎症和胰岛素抵抗的一个关键事件，但是我们对其他免疫细胞类型在这些过程中的扮演的角色知道的很少。
最近，内脏脂肪组织中调节性T细胞的一个独特类群被认为参与控制脂肪组织的炎症状态，因而，也被认为与胰岛素的敏感性相关。
研究表明，过氧化物酶体增生物激活受体γ（PPAR-γ)，作为脂肪细胞分化的一个主要的调节子，被确定为协调内脏脂肪组织调节性T细胞的累积、类型和功能的关键分子。意外发现，噻唑烷二酮药物吡格列酮要想完全恢复小鼠的胰岛素敏感性，内脏脂肪组织调节性T细胞内PPAR-γ的表达是必须的。
这些发现揭示了噻唑烷二酮药物作用的细胞机制，并证明了具有独特功能的调节性T细胞的独立类群能精确地用于治疗疾病。(
生物谷Bioon.com)
doi：10.1038/nature11132PMC:
PMID:
PPAR-γ is a major driver of the accumulation and
phenotype of adipose tissue Treg cells
Daniela Cipolletta，Markus Feuerer，Amy Li，Nozomu Kamei，Jongsoon Lee，Steven E. Shoelson，Christophe Benoist&Diane Mathis
Obesity and type-2 diabetes have increased markedly over the past few decades， in parallel. One of the major links between these two disorders is chronic， low-grade inflammation1. Prolonged nutrient excess promotes the accumulation and activation of leukocytes in visceral adipose tissue (VAT) and ultimately other tissues， leading to metabolic abnormalities such as insulin resistance， type-2 diabetes and fatty-liver disease. Although invasion of VAT by pro-inflammatory macrophages is considered to be a key event driving adipose-tissue inflammation and insulin resistance， little is known about the roles of other immune system cell types in these processes. A unique population of VAT-resident regulatory T (Treg) cells was recently implicated in control of the inflammatory state of adipose tissue and， thereby， insulin sensitivity2. Here we identify peroxisome proliferator-activated receptor (PPAR)-γ， the ‘master regulator’ of adipocyte differentiation， as a crucial molecular orchestrator of VAT Treg cell accumulation， phenotype and function. Unexpectedly， PPAR-γ expression by VAT Treg cells was necessary for complete restoration of insulin sensitivity in obese mice by the thiazolidinedione drug pioglitazone. These findings suggest a previously unknown cellular mechanism for this important class of thiazolidinedione drugs， and provide proof-of-principle that discrete populations of Treg cells with unique functions can be precisely targeted to therapeutic ends.
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