Control of Foxp3 stability through modulation of TET activity

Xiaojing Yue, Sara Trifari, Tarmo Äijö, Ageliki Tsagaratou, William A. Pastor, Jorge A. Zepeda-Martínez, Chan Wang J Lio, Xiang Li, Yun Huang, Pandurangan Vijayanand, Harri Lähdesmäki, Anjana Rao*

*Tämän työn vastaava kirjoittaja

Tutkimustuotos: LehtiartikkeliArticleScientificvertaisarvioitu

147 Sitaatiot (Scopus)
8 Lataukset (Pure)

Abstrakti

Ten-eleven translocation (TET ) enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine and other oxidized methylcytosines, intermediates in DNA demethylation. In this study, we examine the role of TET proteins in regulating Foxp3, a transcription factor essential for the development and function of regulatory T cells (T reg cells), a distinct lineage of CD4+ T cells that prevent autoimmunity and maintain immune homeostasis. We show that during T reg cell development in the thymus, TET proteins mediate the loss of 5mC in T reg cell-specific hypomethylated regions, including CNS1 and CNS2, intronic cis-regulatory elements in the Foxp3 locus. Similar to CNS2-deficient T reg cells, the stability of Foxp3 expression is markedly compromised in T reg cells from Tet2/Tet3 double-deficient mice. Vitamin C potentiates TET activity and acts through Tet2/ Tet3 to increase the stability of Foxp3 expression in TGF -β-induced T reg cells. Our data suggest that targeting TET enzymes with small molecule activators such as vitamin C might increase induced T reg cell efficacy.

AlkuperäiskieliEnglanti
Sivut377-397
Sivumäärä21
JulkaisuJOURNAL OF EXPERIMENTAL MEDICINE
Vuosikerta213
Numero3
DOI - pysyväislinkit
TilaJulkaistu - 2016
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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