Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.
Cutting edge: distinct glycolytic and lipid oxidative metabolic programs are essential for effector and regulatory CD4+ T cell subsets.
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DOI：
10.4049/jimmunol.1003613
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发表时间：
2011-03-15
期刊：
影响因子：
--
通讯作者：
Rathmell JC
中科院分区：
文献类型：
--
作者：
Michalek RD;Gerriets VA;Jacobs SR;Macintyre AN;MacIver NJ;Mason EF;Sullivan SA;Nichols AG;Rathmell JC
受刺激的CD4 + T淋巴细胞可分化为具有特定免疫作用的效应T细胞（Teff）或诱导性调节T细胞（Treg）亚群。我们发现Teff和Treg需要不同的代谢程序来支持这些功能。Th1、Th2和Th17细胞表面葡萄糖转运蛋白Glut1表达水平高，且糖酵解程度高。相比之下，Treg的Glut1表达水平低，且脂质氧化速率高。与糖酵解和脂质氧化分别促进Teff和Treg相符的是，在Glut1转基因小鼠中Teff选择性增加且依赖于葡萄糖代谢，而Treg激活了AMP活化蛋白激酶且依赖于脂质氧化。重要的是，在哮喘模型中，AMP活化蛋白激酶的刺激足以降低Glut1并增加Treg的产生。这些数据表明，CD4 + T细胞亚群需要不同的代谢程序，这些程序可在体内进行调控，以控制炎症性疾病中Treg和Teff的发育。
Stimulated CD4+ T lymphocytes can differentiate into effector T cell (Teff) or inducible regulatory T cell (Treg) subsets with specific immunological roles. We show that Teff and Treg require distinct metabolic programs to support these functions. Th1, Th2, and Th17 cells expressed high surface levels of the glucose transporter Glut1 and were highly glycolytic. Treg, in contrast, expressed low levels of Glut1 and had high lipid oxidation rates. Consistent with glycolysis and lipid oxidation promoting Teff and Treg, respectively, Teff were selectively increased in Glut1 transgenic mice and reliant on glucose metabolism, whereas Treg had activated AMP-activated protein kinase and were dependent on lipid oxidation. Importantly, AMP-activated protein kinase stimulation was sufficient to decrease Glut1 and increase Treg generation in an asthma model. These data demonstrate that CD4+ T cell subsets require distinct metabolic programs that can be manipulated in vivo to control Treg and Teff development in inflammatory diseases.
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DOI：
10.1165/rcmb.2009-0198oc
发表时间：
2010-09-01
影响因子：
6.4
作者：
Hollingsworth, John W.;Theriot, Barbara S.;Walker, Julia K. L.
通讯作者：
Walker, Julia K. L.
影响因子：
64.8
作者：
Araki, Koichi;Turner, Alexandra P.;Shaffer, Virginia Oliva;Gangappa, Shivaprakash;Keller, Susanne A.;Bachmann, Martin F.;Larsen, Christian P.;Ahmed, Rafi
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影响因子：
10.5
作者：
Lum, Julian J.;Bui, Thi;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
4.4
作者：
Cham, CM;Gajewski, TF
通讯作者：
Gajewski, TF
DOI：
10.1126/science.1191996
发表时间：
2010-09-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Rubtsov YP;Niec RE;Josefowicz S;Li L;Darce J;Mathis D;Benoist C;Rudensky AY
通讯作者：
Rudensky AY