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Whole‐genome analysis of TET dioxygenase function in regulatory T cells
Author(s) -
Yue Xiaojing,
SamaniegoCastruita Daniela,
GonzálezAvalos Edahí,
Li Xiang,
Barwick Benjamin G,
Rao Anjana
Publication year - 2021
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202152716
Subject(s) - stat5 , epigenetics , biology , chromatin , foxp3 , transcription factor , microbiology and biotechnology , cellular differentiation , gene , immune system , genetics , signal transduction
TET methylcytosine dioxygenases are essential for the stability and function of regulatory T cells (Treg cells), which maintain immune homeostasis and self‐tolerance and express the lineage‐determining transcription factor Foxp3. Here, we use whole‐genome analyses to show that the transcriptional program and epigenetic features (DNA modification, chromatin accessibility) of Treg cells are attenuated in the absence of Tet2 and Tet3. Conversely, the addition of the TET activator vitamin C during TGFβ‐induced iTreg cell differentiation in vitro potentiates the expression of Treg signature genes and alters the epigenetic landscape to better resemble that of Treg cells generated in vivo . Vitamin C enhances IL‐2 responsiveness in iTreg cells by increasing IL2Rα expression, STAT5 phosphorylation, and STAT5 binding, mimicking the IL‐2/STAT5 dependence of Treg cells generated in vivo . In summary, TET proteins play essential roles in maintaining Treg molecular features and promoting their dependence on IL‐2. TET activity during endogenous Treg development and potentiation of TET activity by vitamin C during iTreg differentiation are necessary to maintain the transcriptional and epigenetic features of Treg cells.