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转录因子 EB 协调环境线索调节 T 调节细胞的线粒体适应性和功能。

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

机构信息

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

出版信息

Proc Natl Acad Sci U S A. 2022 Aug 2;119(31):e2205469119. doi: 10.1073/pnas.2205469119. Epub 2022 Jul 27.

DOI:10.1073/pnas.2205469119
PMID:35895684
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9351480/
Abstract

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4 T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

摘要

调节性 T 细胞（Treg）对于自身耐受至关重要，但它们不利于抑制宿主抗肿瘤免疫。Treg 细胞如何适应环境信号来协调其体内平衡和功能仍知之甚少。在这里，我们发现转录因子 EB（TFEB）在 CD4 T 细胞中受到宿主营养剥夺或白细胞介素（IL）-2 的诱导。TFEB 在 Treg 细胞中的缺失导致在癌症和自身免疫性疾病的小鼠模型中 Treg 细胞的积累减少和功能受损。TFEB 内在地调节 Treg 细胞分化和线粒体功能相关的基因，同时它独立于其在自噬中的既定作用来抑制促炎细胞因子的表达。这种协调作用对于 Treg 细胞中线粒体完整性和适当的脂质代谢是必需的。这些发现确定了 TFEB 作为协调 Treg 产生和功能的关键调节剂，这可能有助于 T 细胞对局部环境线索的适应性反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/3ac985c00c2d/pnas.2205469119fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/909a74c19629/pnas.2205469119fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/2c5b029c18e3/pnas.2205469119fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/8b1cdd354ce5/pnas.2205469119fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/08cdb0fe7ec4/pnas.2205469119fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/bdca2bdef837/pnas.2205469119fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/2b04e0e379e2/pnas.2205469119fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/3ac985c00c2d/pnas.2205469119fig07.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/909a74c19629/pnas.2205469119fig01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/2c5b029c18e3/pnas.2205469119fig02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/8b1cdd354ce5/pnas.2205469119fig03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/08cdb0fe7ec4/pnas.2205469119fig04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/bdca2bdef837/pnas.2205469119fig05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/2b04e0e379e2/pnas.2205469119fig06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fa7/9351480/3ac985c00c2d/pnas.2205469119fig07.jpg

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