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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE141152 | GEO | 2021/07/19

REPOSITORIES: GEO

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The role of Vitamin C and TET dioxygenases in genome-wide features of regulatory T cells [WGBS]

Project description:TET enzymes are essential for the stability and function of regulatory T cells (Tregs), which maintain immune homeostasis and self-tolerance and express the lineage-determining transcription factor Foxp3. We previously showed that Vitamin C acts through TET enzymes to maintain the demethylated status of CNS2, a key intronic enhancer of the Foxp3 gene that is essential for the stability of Foxp3 expression both in vivo and in vitro. Here we show that Vitamin C enables genome-wide features of “induced” T regulatory cells (iTregs) in vitro that overlap with those induced by TET proteins during Treg differentiation in vivo. Vitamin C enhances IL-2 responsiveness in iTregs by increasing phospho-STAT5 levels, STAT5 occupancy and DNA demethylation at key Treg-specific enhancers, and maintains the stable expression of Treg-specific genes including Foxp3 and Il2ra. Our data will be relevant to future studies of the association between plasma Vitamin C levels, Treg function and autoimmunity in humans.

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TET family dioxygenases and the TET activator vitamin C in immune responses and cancer.

Project description:Vitamin C serves as a cofactor for Fe(II) and 2-oxoglutarate-dependent dioxygenases including TET family enzymes, which catalyze the oxidation of 5-methylcytosine into 5-hydroxymethylcytosine and further oxidize methylcytosines. Loss-of-function mutations in epigenetic regulators such as TET genes are prevalent in hematopoietic malignancies. Vitamin C deficiency is frequently observed in cancer patients. In this review, we discuss the role of vitamin C and TET proteins in cancer, with a focus on hematopoietic malignancies, T regulatory cells, and other immune system cells.

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