Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease
Gut intraepithelial T cells calibrate metabolism and accelerate cardiovascular disease
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DOI：
10.1038/s41586-018-0849-9
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发表时间：
2019-02-07
期刊：
影响因子：
64.8
通讯作者：
Swirski, Filip K.
中科院分区：
文献类型：
--
作者：
He, Shun;Kahles, Florian;Swirski, Filip K.
对食物摄入的生化反应必须精确调节。由于摄入的糖和脂肪可以进入许多合成代谢和分解代谢途径（1），我们的身体如何处理营养物质取决于战略定位的代谢传感器，这些传感器将膳食的内在营养价值与中间代谢联系起来。在这里，我们描述了一个免疫细胞的子集-整合素β 7（+）天然肠上皮内T淋巴细胞（天然IEL）-这是分散在整个小肠的肠上皮细胞层，并调节全身代谢。缺乏天然IEL的整合素β 7（-）小鼠代谢过度活跃，并且当喂食高脂肪和高糖饮食时，对肥胖、高胆固醇血症、高血压、糖尿病和动脉粥样硬化有抵抗力。此外，我们发现，在缺乏天然IEL的情况下，心血管疾病的保护作用取决于肠内分泌衍生的肠促胰岛素GLP-1（2），其通常由IEL通过GLP-1受体的表达控制。在该代谢控制系统中，IEL通过充当限制GLP-1生物利用度的看门人来调节肠内分泌活性。虽然IEL的功能可能在食物稀缺时被证明是有利的，但当今过量的高脂肪和高糖饮食使这一代谢检查点对健康有害。
The biochemical response to food intake must be precisely regulated. Because ingested sugars and fats can feed into many anabolic and catabolic pathways(1), how our bodies handle nutrients depends on strategically positioned metabolic sensors that link the intrinsic nutritional value of a meal with intermediary metabolism. Here we describe a subset of immune cells-integrin beta 7(+) natural gut intraepithelial T lymphocytes (natural IELs)-that is dispersed throughout the enterocyte layer of the small intestine and that modulates systemic metabolism. Integrin beta 7(-) mice that lack natural IELs are metabolically hyperactive and, when fed a high-fat and high-sugar diet, are resistant to obesity, hypercholesterolaemia, hypertension, diabetes and atherosclerosis. Furthermore, we show that protection from cardiovascular disease in the absence of natural IELs depends on the enteroendocrine-derived incretin GLP-1(2), which is normally controlled by IELs through expression of the GLP-1 receptor. In this metabolic control system, IELs modulate enteroendocrine activity by acting as gatekeepers that limit the bioavailability of GLP-1. Although the function of IELs may prove advantageous when food is scarce, present-day overabundance of diets high in fat and sugar renders this metabolic checkpoint detrimental to health.