The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.
The glucose transporter Glut1 is selectively essential for CD4 T cell activation and effector function.
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DOI：
10.1016/j.cmet.2014.05.004
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发表时间：
2014-07-01
期刊：
影响因子：
29
通讯作者：
Rathmell JC
中科院分区：
文献类型：
--
作者：
Macintyre AN;Gerriets VA;Nichols AG;Michalek RD;Rudolph MC;Deoliveira D;Anderson SM;Abel ED;Chen BJ;Hale LP;Rathmell JC
CD4T细胞的活化导致快速增殖和分化为调节或调节免疫的效应细胞(TEF)或调节性细胞(Treg)。尽管TJeff和Treg在体外更喜欢不同的糖酵解或氧化代谢程序，但在体内控制T细胞葡萄糖摄取和代谢的要求和机制却知之甚少。尽管有多种葡萄糖转运蛋白的表达，但Glut1缺乏会选择性地损害胸腺细胞和胸腺细胞的代谢和功能。静息T细胞是正常的，直到被激活，当Glut1缺乏阻止葡萄糖摄取和糖酵解增加，生长，增殖，并减少细胞存活和TJeff分化。重要的是，Glut1缺乏降低了Tef的膨胀和在体内诱导炎性疾病的能力。相反，Treg在体内得到了丰富，似乎在功能上不受Glut1缺乏的影响，并且能够抑制TJeff，而与Glut1的表达无关。这些数据表明，在体内对Glut1的选择性需求在代谢重编程的CD4T细胞激活和T细胞的扩增和存活。
CD4 T cell activation leads to rapid proliferation and differentiation into effector (Teff) or regulatory (Treg) cells that mediate or control immunity. While Teff and Treg prefer distinct glycolytic or oxidative metabolic programs in vitro, requirements and mechanisms that control T cell glucose uptake and metabolism in vivo are poorly understood. Despite expression of multiple glucose transporters, Glut1-deficiency selectively impaired metabolism and function of thymocytes and Teff. Resting T cells were normal until activated, when Glut1-deficiency prevented increased glucose uptake and glycolysis, growth, proliferation, and decreased cell survival and Teff differentiation. Importantly, Glut1-deficiency decreased Teff expansion and ability to induce inflammatory disease in vivo. Treg, in contrast, were enriched in vivo and appeared functionally unaffected by Glut1-deficiency and able to suppress Teff irrespective of Glut1 expression. These data show a selective in vivo requirement for Glut1 in metabolic reprogramming of CD4 T cell activation and Teff expansion and survival.
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DOI：
10.4049/jimmunol.0902593
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacobs SR;Michalek RD;Rathmell JC
通讯作者：
Rathmell JC
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
4.9
作者：
Hale, LP;Gottfried, MR;Swidinski, A
通讯作者：
Swidinski, A
DOI：
10.1152/ajpendo.00083.2011
发表时间：
2011-06-01
影响因子：
5.1
作者：
Rudolph, Michael C.;Russell, Tanya D.;Anderson, Steven M.
通讯作者：
Anderson, Steven M.
影响因子：
7.8
作者：
Carrette F;Surh CD
通讯作者：
Surh CD