Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.
Leptin directly promotes T-cell glycolytic metabolism to drive effector T-cell differentiation in a mouse model of autoimmunity.
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瘦素直接促进T细胞糖酵解代谢，以驱动自身免疫模型中的效应T细胞分化。
DOI：
10.1002/eji.201545861
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发表时间：
2016-08
影响因子：
5.4
通讯作者：
MacIver, Nancie J.
中科院分区：
文献类型：
--
作者：
Gerriets, Valerie A.;Danzaki, Keiko;Kishton, Rigel J.;Eisner, William;Nichols, Amanda G.;Saucillo, Donte C.;Shinohara, Mari L.;MacIver, Nancie J.
激活后，T细胞的生长、增殖和功能需要能量。效应T细胞，如Th1和Th17，利用高水平的葡萄糖摄取和糖酵解来刺激增殖和功能。相反，Treg需要氧化代谢来支持抑制功能。目前尚不清楚在营养不良、营养有限和循环瘦素水平低的情况下，TJeff/Treg代谢是如何改变的。因此，我们研究了营养不良和相关的低肽血症对TREG和TREF的影响。我们发现，营养不良相关的低蛋白血症和T细胞特异性瘦素受体基因敲除都抑制了Teff数、功能和葡萄糖代谢，但不改变Treg代谢或抑制功能。利用自身免疫模型EAE，我们证实了禁食诱导的低肽血症改变了体内的TJeff，但不改变了Treg，葡萄糖代谢和功能，导致了疾病严重程度的降低。为了探索可能的机制，我们检测了Th17分化和Treg糖代谢的关键调节因子HIF-1α，发现在T细胞特异性瘦素受体敲除的Th17细胞和禁食的EAE小鼠的Tef细胞中，HIF-1α的表达降低，但在Treg中没有变化。综上所述，这些数据显示了一种选择性的、细胞内的需求，需要瘦素来上调糖代谢并维持TEFF的功能，而不是Treg。
Upon activation, T cells require energy for growth, proliferation and function. Effector T cells (Teff), such as Th1 and Th17, utilize high levels of glucose uptake and glycolysis to fuel proliferation and function. In contrast, Treg instead require oxidative metabolism to fuel suppressive function. It remains unknown how Teff/Treg metabolism is altered in settings of malnutrition, when nutrients are limited and circulating leptin levels are low. We therefore examined the role of malnutrition and associated hypoleptinemia on Teff versus Treg. We found that both malnutrition-associated hypoleptinemia and T cell-specific leptin receptor knockout suppressed Teff number, function, and glucose metabolism, but did not alter Treg metabolism or suppressive function. Using the autoimmune model EAE, we confirmed that fasting-induced hypoleptinemia altered Teff, but not Treg, glucose metabolism and function in vivo, leading to decreased disease severity. To explore potential mechanisms, we examined HIF-1α, a key regulator of Th17 differentiation and Teff glucose metabolism, and found HIF-1α expression was decreased in T cell-specific leptin receptor knockout Th17 cells, and in Teff cells from fasted EAE mice, but was unchanged in Treg. Altogether, these data demonstrate a selective, cell-intrinsic requirement for leptin to upregulate glucose metabolism and maintain function in Teff, but not Treg.
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影响因子：
64.5
作者：
Ivanov, Ivaylo I.;McKenzie, Brent S.;Littman, Dan R.
通讯作者：
Littman, Dan R.
影响因子：
29
作者：
Macintyre AN;Gerriets VA;Nichols AG;Michalek RD;Rudolph MC;Deoliveira D;Anderson SM;Abel ED;Chen BJ;Hale LP;Rathmell JC
通讯作者：
Rathmell JC
DOI：
10.4049/jimmunol.1102835
发表时间：
2012-03-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Liu Y;Yu Y;Matarese G;La Cava A
通讯作者：
La Cava A
影响因子：
32.4
作者：
De Rosa, Veronica;Procaccini, Claudio;Matarese, Giuseppe
通讯作者：
Matarese, Giuseppe
影响因子：
15.9
作者：
De Rosa, V;Procaccini, C;Matarese, G
通讯作者：
Matarese, G