Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes
Costimulation of type-2 innate lymphoid cells by GITR promotes effector function and ameliorates type 2 diabetes
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DOI：
10.1038/s41467-019-08449-x
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发表时间：
2019-02-12
影响因子：
16.6
通讯作者：
Akbari, Omid
中科院分区：
文献类型：
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作者：
Galle-Treger, Lauriane;Sankaranarayanan, Ishwarya;Akbari, Omid
代谢综合征的特征是葡萄糖稳态紊乱和低度全身炎症的发展，这增加了发展为2型糖尿病（T2DM）的风险。2型先天淋巴样细胞（ILC2s）是最近发现的一种分泌Th2细胞因子的免疫群体。虽然先前的研究表明ILC2s如何在脂肪组织的代谢稳态调节中发挥关键作用，但能够调节ILC2激活的治疗靶点尚未确定。在这里，我们发现GITR， TNF超家族的一员，在小鼠和人类ILC2s上都表达。引人注目的是，我们证明激活的ILC2s参与GITR可改善葡萄糖稳态，从而防止胰岛素抵抗的发生并改善已建立的胰岛素抵抗。总之，这些结果突出了GITR作为一种新的治疗T2DM的分子的关键作用，以及它作为激活ILC2s的免疫检查点的基本作用。
Metabolic syndrome is characterized by disturbances in glucose homeostasis and the development of low-grade systemic inflammation, which increase the risk to develop type 2 diabetes mellitus (T2DM). Type-2 innate lymphoid cells (ILC2s) are a recently discovered immune population secreting Th2 cytokines. While previous studies show how ILC2s can play a critical role in the regulation of metabolic homeostasis in the adipose tissue, a therapeutic target capable of modulating ILC2 activation has yet to be identified. Here, we show that GITR, a member of the TNF superfamily, is expressed on both murine and human ILC2s. Strikingly, we demonstrate that GITR engagement of activated, but not naive, ILC2s improves glucose homeostasis, resulting in both protection against insulin resistance onset and amelioration of established insulin-resistance. Together, these results highlight the critical role of GITR as a novel therapeutic molecule against T2DM and its fundamental role as an immune checkpoint for activated ILC2s.