The role of AMP-activated protein kinase in GVHD-causing T cells.

Immunometabolism (Cobham (Surrey, England)) Pub Date : 2022-10-07 eCollection Date: 2022-10-01 DOI:10.1097/IN9.0000000000000009
Archana Ramgopal, Lee-Kai Sun, Craig A Byersdorfer
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Abstract

Allogeneic stem cell transplantation is a curative therapy for multiple hematologic disorders. However, this life-saving procedure is often complicated by acute graft-versus-host disease (GVHD), where donor T cells attack tissues in the recipient's skin, liver, and gastrointestinal tract. Previous research has demonstrated that GVHD-causing T cells undergo significant metabolic reprogramming during disease pathogenesis, with an increased reliance on oxidative metabolism. This dependence makes metabolic modulation a potential approach to treat and/or prevent GVHD. Here, we provide an overview on the metabolic changes adopted by allogeneic T cells during disease initiation, highlighting the role played by AMP-activated protein kinase (AMPK) and identifying ways in which these insights might be leveraged to therapeutic advantage clinically.

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AMP激活蛋白激酶在致GVHD T细胞中的作用
异体干细胞移植是治疗多种血液病的一种疗法。然而,急性移植物抗宿主疾病(GVHD)往往使这一挽救生命的过程变得复杂,因为供体T细胞会攻击受体的皮肤、肝脏和胃肠道组织。以往的研究表明,导致 GVHD 的 T 细胞在疾病发病过程中经历了显著的代谢重编程,对氧化代谢的依赖性增加。这种依赖性使代谢调节成为治疗和/或预防 GVHD 的潜在方法。在这里,我们概述了异体 T 细胞在疾病发生过程中发生的代谢变化,强调了 AMP 激活蛋白激酶 (AMPK) 所起的作用,并指出了在临床上如何利用这些见解来发挥治疗优势。
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