PD-1 Is Involved in the Dysregulation of Type 2 Innate Lymphoid Cells in a Murine Model of Obesity
PD-1 Is Involved in the Dysregulation of Type 2 Innate Lymphoid Cells in a Murine Model of Obesity
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DOI：
10.1016/j.celrep.2018.10.091
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发表时间：
2018-11-20
期刊：
影响因子：
8.8
通讯作者：
Moser, Muriel
中科院分区：
文献类型：
--
作者：
Oldenhove, Guillaume;Boucquey, Elodie;Moser, Muriel
最近的观察清楚地强调了2型先天淋巴细胞在维持人类和小鼠脂肪组织稳态中的关键作用。该细胞群通过维持富含嗜酸性粒细胞和交替激活的巨噬细胞的Th 2倾向环境，直接和间接地促进肥胖和限制肥胖。因此，2型先天淋巴样细胞（ILC 2）的数量和功能在肥胖个体中严重受损。在这项工作中，我们确定PD-1-PD-L1途径是导致ILC 2在高脂肪喂养后不稳定的一个因素，从而导致组织代谢受损。肿瘤坏死因子（TNF）似乎起着核心作用，触发ILC 2上的白细胞介素-33（IL-33）依赖性PD-1表达，并招募和激活PD-L1（hi）M1巨噬细胞。PD-1阻断部分恢复2型先天性轴，提高了恢复组织稳态的可能性。
Recent observations clearly highlight the critical role of type 2 innate lymphoid cells in maintaining the homeostasis of adipose tissues in humans and mice. This cell population promotes beiging and limits adiposity directly and indirectly by sustaining a Th2-prone environment enriched in eosinophils and alternatively activated macrophages. Accordingly, the number and function of type 2 innate lymphoid cells (ILC2s) are strongly impaired in obese individuals. In this work, we identify the PD-1-PD-L1 pathway as a factor leading to ILC2 destabilization upon high-fat feeding resulting in impaired tissue metabolism. Tumor necrosis factor (TNF) appears to play a central role, triggering interleukin-33 (IL-33)-dependent PD-1 expression on ILC2s and recruiting and activating PD-L1(hi) M1 macrophages. PD-1 blockade partially restores the type 2 innate axis, raising the possibility of restoring tissue homeostasis.