Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis
Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis
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DOI：
10.1016/j.celrep.2021.109921
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发表时间：
2021-11-09
期刊：
影响因子：
8.8
通讯作者：
Endo, Yusuke
中科院分区：
文献类型：
--
作者：
Kanno, Toshio;Nakajima, Takahiro;Endo, Yusuke
调节性 T (Treg) 细胞对于免疫耐受和免疫稳态至关重要。 Treg 细胞强烈依赖线粒体代谢并表现出较低水平的糖酵解。然而，人们对脂质代谢在 Treg 细胞稳态调节中的作用知之甚少。 ACSL 酰基辅酶 A (CoA) 合酶家族的一些成员在 T 细胞中表达，但其功能仍不清楚。 RNA测序和蛋白质组分析相结合表明ACSL成员Acsbg1在Treg细胞中选择性表达。我们发现 Acsbg1 的基因缺失不仅会导致线粒体功能障碍，还会抑制其他代谢途径。外源性补充 Acsbg1 缺陷的 Treg 细胞油酰辅酶 A 可恢复 Treg 代谢特征的表型。此外，ST2+效应Treg细胞中的这条通路增强了气道炎症中的免疫抑制能力。因此，Acsbg1 作为控制 Treg 细胞稳态和肺部炎症消退的代谢检查点。
Regulatory T (Treg) cells are critical for immunological tolerance and immune homeostasis. Treg cells strongly rely on mitochondrial metabolism and show a lower level of glycolysis. However, little is known about the role of lipid metabolism in the regulation of Treg cell homeostasis. Some members of the ACSL family of acyl-coenzyme A (CoA) synthases are expressed in T cells, but their function remains unclear. A combination of RNAsequencing and proteome analyses shows that Acsbg1, a member of ACSL, is selectively expressed in Treg cells. We show that the genetic deletion of Acsbg1 not only causes mitochondrial dysfunction, but it also dampens other metabolic pathways. The extrinsic supplementation of Acsbg1-deficient Treg cells with oleoyl-CoA restores the phenotype of the Treg metabolic signature. Furthermore, this pathway in ST2+ effector Treg cells enhances immunosuppressive capacity in airway inflammation. Thus, Acsbg1 serves as a metabolic checkpoint governing Treg cell homeostasis and the resolution of lung inflammation.