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

First Author  Xia M Year  2022
Journal  Proc Natl Acad Sci U S A Volume  119
Issue  31 Pages  e2205469119
PubMed ID  35895684 Mgi Jnum  J:336031
Mgi Id  MGI:7430680 Doi  10.1073/pnas.2205469119
Citation  Xia M, et al. (2022) Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function. Proc Natl Acad Sci U S A 119(31):e2205469119
abstractText  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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