Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming.
Very-low-carbohydrate diet enhances human T-cell immunity through immunometabolic reprogramming.
复制标题
极低碳水化合物饮食通过免疫代谢重编程增强人类T细胞免疫。
DOI：
10.15252/emmm.202114323
复制
发表时间：
2021-08-09
影响因子：
11.1
通讯作者：
Kreth S
中科院分区：
文献类型：
--
作者：
Hirschberger S;Strauß G;Effinger D;Marstaller X;Ferstl A;Müller MB;Wu T;Hübner M;Rahmel T;Mascolo H;Exner N;Heß J;Kreth FW;Unger K;Kreth S
极低碳水化合物饮食触发内源性产生酮体作为替代能量底物。目前尚未证实酮体对人体免疫有积极影响的假设。我们在使用原代人T细胞的体外模型和招募健康志愿者的免疫营养干预研究中研究了这一主题。我们发现酮体深刻地影响人类T细胞反应。CD4+、CD8+和调节性T细胞能力显著增强，T记忆细胞形成增强。RNAseq和功能代谢分析揭示了一个基本的免疫代谢重编程，以响应酮有利于线粒体氧化代谢。这赋予了优越的呼吸储备、细胞能量供应和活性氧信号。我们的数据表明，极低碳水化合物饮食是改善人类T细胞免疫的临床工具。需要重新思考营养和饮食干预在现代医学中的价值。生酮饮食（KD）的特点是碳水化合物的摄取非常有限，导致内源性酮体的产生。本研究确定KD是一种有效的营养免疫代谢干预，可重编程人类T细胞免疫代谢，有利于线粒体氧化磷酸化，从而增强效应和调节性T细胞免疫能力，并启动人类T细胞形成记忆细胞。
Very‐low‐carbohydrate diet triggers the endogenous production of ketone bodies as alternative energy substrates. There are as yet unproven assumptions that ketone bodies positively affect human immunity. We have investigated this topic in an in vitro model using primary human T cells and in an immuno‐nutritional intervention study enrolling healthy volunteers. We show that ketone bodies profoundly impact human T‐cell responses. CD4+, CD8+, and regulatory T‐cell capacity were markedly enhanced, and T memory cell formation was augmented. RNAseq and functional metabolic analyses revealed a fundamental immunometabolic reprogramming in response to ketones favoring mitochondrial oxidative metabolism. This confers superior respiratory reserve, cellular energy supply, and reactive oxygen species signaling. Our data suggest a very‐low‐carbohydrate diet as a clinical tool to improve human T‐cell immunity. Rethinking the value of nutrition and dietary interventions in modern medicine is required. Ketogenic diet (KD) is characterized by a very limited uptake of carbohydrates, resulting in endogenous production of ketone bodies. This study identifies KD as a potent nutritional immunometabolic intervention to reprogram human T cell immunometabolism, favouring mitochondrial oxidative phosphorylation, thus enhancing both effector and regulatory T cell immune capacity and priming human T cells towards memory cell formation.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
5
作者：
Archer E;Lavie CJ;Hill JO
通讯作者：
Hill JO
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：
32.4
作者：
Jones, Russell G.;Bui, Thi;Thompson, Craig B.
通讯作者：
Thompson, Craig B.
影响因子：
4.4
作者：
Cohen, Evan;Cragg, Michael;Zhou, Bin
通讯作者：
Zhou, Bin