5月16日，Nature在線發(fā)表了哈佛醫(yī)學(xué)院微生物與免疫學(xué)系等機構(gòu)的一篇題為PPAR-γ is a major driver of the accumulation and phenotype of adipose tissue Treg cells 的研究論文,，揭示了噻唑烷二酮藥物作用疾病的細(xì)胞機制,，并證明了具有獨特功能的調(diào)節(jié)性T細(xì)胞的獨立類群能精確地用于治療疾病。
在過去的幾十年來,，肥胖和Ⅱ型糖尿病同步急劇增加,。這兩種代謝紊亂癥的一個最主要聯(lián)系是同屬于慢性低級炎癥,。持續(xù)的營養(yǎng)過剩促使內(nèi)臟脂肪組織內(nèi)白細(xì)胞的累積和激活，并延伸到其他組織,，最終導(dǎo)致胰島素抵抗,、Ⅱ型糖尿病和脂肪肝等代謝異常疾病,。
雖然促炎癥巨噬細(xì)胞入侵內(nèi)臟脂肪組織被認(rèn)為是驅(qū)動脂肪組織炎癥和胰島素抵抗的一個關(guān)鍵事件,，但是我們對其他免疫細(xì)胞類型在這些過程中的扮演的角色知道的很少。
最近,，內(nèi)臟脂肪組織中調(diào)節(jié)性T細(xì)胞的一個獨特類群被認(rèn)為參與控制脂肪組織的炎癥狀態(tài),，因而，也被認(rèn)為與胰島素的敏感性相關(guān),。
研究表明,，過氧化物酶體增生物激活受體γ（PPAR-γ)，作為脂肪細(xì)胞分化的一個主要的調(diào)節(jié)子,，被確定為協(xié)調(diào)內(nèi)臟脂肪組織調(diào)節(jié)性T細(xì)胞的累積,、類型和功能的關(guān)鍵分子。意外發(fā)現(xiàn),，噻唑烷二酮藥物吡格列酮要想完全恢復(fù)小鼠的胰島素敏感性,，內(nèi)臟脂肪組織調(diào)節(jié)性T細(xì)胞內(nèi)PPAR-γ的表達(dá)是必須的。
這些發(fā)現(xiàn)揭示了噻唑烷二酮藥物作用的細(xì)胞機制,，并證明了具有獨特功能的調(diào)節(jié)性T細(xì)胞的獨立類群能精確地用于治療疾病,。(生物谷Bioon.com)
doi：10.1038/nature11132
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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.
