Metabolic reprogramming in macrophages and dendritic cells in innate immunity.
Metabolic reprogramming in macrophages and dendritic cells in innate immunity.
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作者：
巨噬细胞和树突状细胞（DC）通过促炎刺激的活化导致它们经历朝向糖酵解和远离氧化磷酸化（OXPHOS）的代谢转换，类似于肿瘤中的瓦尔堡效应。然而，直到最近才更详细地阐明了这种代谢重编程的机制。转录因子缺氧诱导因子-1 α（hypoxia-inducible factor-1α，HIF-1α）在缺氧和常氧条件下均发挥重要作用。柠檬酸盐从三羧酸（TCA）循环中的退出已被证明对巨噬细胞和DC中的脂质生物合成至关重要。干扰这一过程实际上消除了DC激活T细胞的能力。另一种TCA循环中间体琥珀酸可激活HIF-1α并促进炎症基因表达。这些新的见解使我们更深入地了解了代谢重编程在先天免疫中的作用。
Activation of macrophages and dendritic cells (DCs) by pro-inflammatory stimuli causes them to undergo a metabolic switch towards glycolysis and away from oxidative phosphorylation (OXPHOS), similar to the Warburg effect in tumors. However, it is only recently that the mechanisms responsible for this metabolic reprogramming have been elucidated in more detail. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role under conditions of both hypoxia and normoxia. The withdrawal of citrate from the tricarboxylic acid (TCA) cycle has been shown to be critical for lipid biosynthesis in both macrophages and DCs. Interference with this process actually abolishes the ability of DCs to activate T cells. Another TCA cycle intermediate, succinate, activates HIF-1α and promotes inflammatory gene expression. These new insights are providing us with a deeper understanding of the role of metabolic reprogramming in innate immunity.
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DOI：
10.4049/jimmunol.1001567
发表时间：
2011-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Belikoff BG;Hatfield S;Georgiev P;Ohta A;Lukashev D;Buras JA;Remick DG;Sitkovsky M
通讯作者：
Sitkovsky M
影响因子：
20.3
作者：
Everts, Bart;Amiel, Eyal;Pearce, Edward J.
通讯作者：
Pearce, Edward J.
影响因子：
4.8
作者：
Ak, Prashanth;Levine, Arnold J.
通讯作者：
Levine, Arnold J.
影响因子：
7.3
作者：
Doulias PT;Tenopoulou M;Greene JL;Raju K;Ischiropoulos H
通讯作者：
Ischiropoulos H
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.