AMPK 扩增 IL2-STAT5 信号通路以维持老年小鼠调节性 T 细胞的稳定性。
AMPK Amplifies IL2-STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice.
机构信息
College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea.
Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu 41944, Korea.
出版信息
Int J Mol Sci. 2022 Oct 16;23(20):12384. doi: 10.3390/ijms232012384.
AMP-activated protein kinase (AMPK), an important regulator of the aging process, is expressed in various immune cells. However, its role in regulatory T cell (Treg) stability during aging is poorly understood. Here, we addressed the role of AMPK in Treg function and stability during aging by generating Treg-specific AMPKα1 knockout mice. In this study, we found that AMPKα1-deficient Tregs failed to control inflammation as effectively as normal Tregs did during aging. AMPK knockout from Tregs reduces STAT5 phosphorylation in response to interleukin (IL)-2 stimulation, thereby destabilizing Tregs by decreasing CD25 expression. Thus, our study addressed the role of AMPK in Tregs in sensing IL-2 signaling to amplify STAT5 phosphorylation, which, in turn, supports Treg stability by maintaining CD25 expression and controlling inflamm-aging.
AMP 激活的蛋白激酶 (AMPK) 是衰老过程的重要调节因子，在各种免疫细胞中表达。然而，其在衰老过程中调节性 T 细胞 (Treg) 稳定性中的作用尚不清楚。在这里，我们通过生成 Treg 特异性 AMPKα1 敲除小鼠来研究 AMPK 在 Treg 功能和稳定性中的作用。在这项研究中，我们发现 AMPKα1 缺陷的 Treg 在衰老过程中控制炎症的能力不如正常 Treg 那样有效。Treg 中的 AMPK 敲除会降低白细胞介素 (IL)-2 刺激时的 STAT5 磷酸化，从而通过降低 CD25 表达来破坏 Treg 的稳定性。因此，我们的研究解决了 AMPK 在 Treg 中感应 IL-2 信号以放大 STAT5 磷酸化的作用，这反过来通过维持 CD25 表达和控制炎症衰老来支持 Treg 的稳定性。
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