Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments.
Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments.
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DOI：
10.1038/s41590-020-00848-3
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发表时间：
2021-03
影响因子：
30.5
通讯作者：
Lynch L
中科院分区：
文献类型：
--
作者：
Lopes N;McIntyre C;Martin S;Raverdeau M;Sumaria N;Kohlgruber AC;Fiala GJ;Agudelo LZ;Dyck L;Kane H;Douglas A;Cunningham S;Prendeville H;Loftus R;Carmody C;Pierre P;Kellis M;Brenner M;Argüello RJ;Silva-Santos B;Pennington DJ;Lynch L
代谢编程控制免疫细胞谱系和功能，但对γδ T细胞代谢知之甚少。在这里，我们发现产生干扰素-γ（IFN-γ）或白细胞介素-17（IL-17）的γδ T细胞亚群具有本质上不同的代谢要求。IFN-γ+ γδ T细胞几乎完全依赖于糖酵解，而IL-17+ γδ T细胞强烈参与氧化代谢，线粒体质量和活性增加。这些独特的代谢特征在胸腺发育早期就令人惊讶地被印记，并稳定地维持在外周和肿瘤内。此外，促肿瘤IL-17+ γδ T细胞选择性地显示高脂质摄取和细胞内脂质储存，并且在肥胖症和肥胖小鼠的肿瘤中扩增。相反，葡萄糖补充增强了IFN-γ+ γδ T细胞的抗肿瘤功能，并减少了过继转移后的肿瘤生长。这些发现对效应γδ T细胞的分化及其在癌症免疫治疗中的操作具有重要意义。
Metabolic programming controls immune cell lineages and functions, but little is known about γδ T cell metabolism. Here, we found that γδ T cell subsets making either interferon-γ (IFN-γ) or interleukin-17 (IL-17) have intrinsically distinct metabolic requirements. Whereas IFN-γ+ γδ T cells were almost exclusively dependent on glycolysis, IL-17+ γδ T cells strongly engaged oxidative metabolism, with increased mitochondrial mass and activity. These distinct metabolic signatures were surprisingly imprinted early during thymic development, and were stably maintained in the periphery and within tumors. Moreover, pro-tumoral IL-17+ γδ T cells selectively showed high lipid uptake and intracellular lipid storage, and were expanded in obesity, and in tumors of obese mice. Conversely, glucose supplementation enhanced the anti-tumor functions of IFN-γ+ γδ T cells and reduced tumor growth upon adoptive transfer. These findings have important implications for the differentiation of effector γδ T cells and their manipulation in cancer immunotherapy.
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影响因子：
5.8
作者：
Liberzon, Arthur;Subramanian, Aravind;Mesirov, Jill P.
通讯作者：
Mesirov, Jill P.
影响因子：
16.6
作者：
In TSH;Trotman-Grant A;Fahl S;Chen ELY;Zarin P;Moore AJ;Wiest DL;Zúñiga-Pflücker JC;Anderson MK
通讯作者：
Anderson MK
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
DOI：
10.1084/jem.20131540
发表时间：
2014-02-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Coffey F;Lee SY;Buus TB;Lauritsen JP;Wong GW;Joachims ML;Thompson LF;Zúñiga-Pflücker JC;Kappes DJ;Wiest DL
通讯作者：
Wiest DL
影响因子：
5.4
作者：
Cham, Candace M.;Driessens, Gregory;O'Keefe, James P.;Gajewski, Thomas F.
通讯作者：
Gajewski, Thomas F.