DOI：10.1038/nature14115 中国科研用户发表 作者：Jonathan R. Brestoff
摘要 : 免疫系统现在被认为与遗传因素和环境因素一起涉及到肥胖的形成中。最新研究发现，脂肪组织中的 “2-组先天淋巴样细胞”(ILC2s)是造成小鼠发生肥胖的一个因素。
David Artis及同事在这项研究中显示，ILC2s通过响应于白介素-33生成 “蛋氨酸-脑啡肽”肽在能量平衡中扮演一个关键角色。
Obesity is an increasingly prevalent disease regulated by genetic and environmental factors. Emerging studies indicate that immune cells, including monocytes, granulocytes and lymphocytes, regulate metabolic homeostasis and are dysregulated in obesity1, 2. Group 2 innate lymphoid cells (ILC2s) can regulate adaptive immunity3, 4 and eosinophil and alternatively activated macrophage responses5, and were recently identified in murine white adipose tissue (WAT)5 wher they may act to limit the development of obesity6. However, ILC2s have not been identified in human adipose tissue, and the mechanisms by which ILC2s regulate metabolic homeostasis remain unknown. Here we identify ILC2s in human WAT and demonstrate that decreased ILC2 responses in WAT are a conserved characteristic of obesity in humans and mice. Interleukin (IL)-33 was found to be critical for the maintenance of ILC2s in WAT and in limiting adiposity in mice by increasing caloric expenditure. This was associated with recruitment of uncoupling protein 1 (UCP1)+ beige adipocytes in WAT, a process known as beiging or browning that regulates caloric expenditure7, 8,9. IL-33-induced beiging was dependent on ILC2s, and IL-33 treatment or transfer of IL-33-elicited ILC2s was sufficient to drive beiging independently of the adaptive immune system, eosinophils or IL-4 receptor signalling. We found that ILC2s produce methionine-enkephalin peptides that can act directly on adipocytes to upregulate Ucp1 expression in vitro and that promote beiging in vivo. Collectively, these studies indicate that, in addition to responding to infection or tissue damage, ILC2s can regulate adipose function and metabolic homeostasis in part via production of enkephalin peptides that elicit beiging.
来源： Nature 浏览次数：202