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.
基金：
National Scientific Foundation of China [32070890, 81671539]; Key Special Project of Ministry of Science and Technology, China [2019YFC1316200]; National Natural Science Foundation of China [81725004]
第一作者单位：[1]Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Basic Med, Dept Immunol, Wuhan 430030, Peoples R China
通讯作者：
通讯机构：[4]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Otolaryngol Head & Neck Surg, Wuhan 430022, Peoples R China[5]Fudan Univ, Affiliated Eye Ear Nose & Throat Hosp, Allergy Ctr, Dept Otolaryngol, Shanghai 200031, Peoples R China
推荐引用方式(GB/T 7714)：
Xia Minghui,Zhang Cai,Chen Yufei,et al.Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2022,119(31):doi:10.1073/pnas.2205469119.
APA：
Xia, Minghui,Zhang, Cai,Chen, Yufei,Zhao, Xiujuan,Zhang, Si...&Yang, Xiang-Ping.(2022).Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,119,(31)
MLA：
Xia, Minghui,et al."Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 119..31(2022)
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