Transcription Factor EB Coordinates Environmental Cues to Regulate T Regulatory Cells' Mitochondrial Fitness and Function

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2022 Jul 27

PMID 35895684

Authors

Minghui Xia

Cai Zhang

Yufei Chen

Xiujuan Zhao

Si Zhang

Yang Liu

You Cai

Zhengping Wei

Qiuyang Du

Wenting Yu

Chun Zhou

Hongjun Xiao

Guihua Wang

Xiang Cheng

Heng Mei

Arian Laurence

Jing Wang

Yu Hu

Huabin Li

Xiang-Ping Yang

Affiliations

Soon will be listed here.

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.

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