Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation.
Etomoxir Actions on Regulatory and Memory T Cells Are Independent of Cpt1a-Mediated Fatty Acid Oxidation.
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DOI：
10.1016/j.cmet.2018.06.002
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发表时间：
2018-09-04
期刊：
影响因子：
29
通讯作者：
Berod L
中科院分区：
文献类型：
--
作者：
Raud B;Roy DG;Divakaruni AS;Tarasenko TN;Franke R;Ma EH;Samborska B;Hsieh WY;Wong AH;Stüve P;Arnold-Schrauf C;Guderian M;Lochner M;Rampertaap S;Romito K;Monsale J;Brönstrup M;Bensinger SJ;Murphy AN;McGuire PJ;Jones RG;Sparwasser T;Berod L
T细胞亚群包括效应细胞（Teff）、调节细胞（Treg）和记忆细胞（Treg），其特征在于影响其分化和功能的不同代谢谱。先前的研究表明，长链脂肪酸氧化（LC-FAO）的参与支持Foxp 3 + Treg细胞和T细胞的存活。然而，这方面的证据主要是基于药物etomoxir对LC-FAO的限速酶Cpt 1a的抑制。使用遗传模型来靶向T细胞中的Cpt 1a，我们剖析了LC-FAO在原发性、记忆性和调节性T细胞应答中的作用。在这里，我们表明，ACC 2/Cpt 1a轴在很大程度上是Teff，T细胞或Treg细胞的形成，etomoxir对T细胞分化和功能的影响是独立的Cpt 1a的表达。总之，我们的数据表明，LC-FAO以外的代谢途径促进了T细胞或Treg分化，并提出了涉及线粒体呼吸的依托莫西影响的替代机制。
T cell subsets including effector (Teff), regulatory (Treg) and memory (Tmem) cells are characterized by distinct metabolic profiles that influence their differentiation and function. Previous research suggests that engagement of long-chain fatty acid oxidation (LC-FAO) supports Foxp3+ Treg cell and Tmem cell survival. However, evidence for this is mostly based on inhibition of Cpt1a, the rate limiting enzyme for LC-FAO, with the drug etomoxir. Using genetic models to target Cpt1a specifically in T cells, we dissected the role of LC-FAO in primary, memory and regulatory T cell responses. Here we show that the ACC2/Cpt1a axis is largely dispensable for Teff, Tmem or Treg cell formation, and that the effects of etomoxir on T cell differentiation and function are independent of Cpt1a expression. Together our data argue that metabolic pathways other than LC-FAO fuel Tmem or Treg differentiation and suggest alternative mechanisms for the effects of etomoxir that involve mitochondrial respiration.
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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：
30.5
作者：
Chang CH;Pearce EL
通讯作者：
Pearce EL
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：
29
作者：
Divakaruni AS;Hsieh WY;Minarrieta L;Duong TN;Kim KKO;Desousa BR;Andreyev AY;Bowman CE;Caradonna K;Dranka BP;Ferrick DA;Liesa M;Stiles L;Rogers GW;Braas D;Ciaraldi TP;Wolfgang MJ;Sparwasser T;Berod L;Bensinger SJ;Murphy AN
通讯作者：
Murphy AN
影响因子：
32.4
作者：
Jones, Russell G.;Bui, Thi;Thompson, Craig B.
通讯作者：
Thompson, Craig B.