T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
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Authors
Ohkura, NaganariHamaguchi, Masahide
Morikawa, Hiromasa
Sugimura, Kyoko
Tanaka, Atsushi
Ito, Yoshinaga
Osaki, Motonao
Tanaka, Yoshiaki
Yamashita, Riu
Nakano, Naoko
Huehn, Jochen
Fehling, Hans Joerg
Sparwasser, Tim
Nakai, Kenta
Sakaguchi, Shimon
Issue Date
2012-11-16
Metadata
Show full item recordAbstract
The transcription factor Foxp3 is essential for the development of regulatory T (Treg) cells, yet its expression is insufficient for establishing the Treg cell lineage. Here we showed that Treg cell development was achieved by the combination of two independent processes, i.e., the expression of Foxp3 and the establishment of Treg cell-specific CpG hypomethylation pattern. Both events were induced by T cell receptor stimulation. The Treg cell-type CpG hypomethylation began in the thymus and continued to proceed in the periphery and could be fully established without Foxp3. The hypomethylation was required for Foxp3(+) T cells to acquire Treg cell-type gene expression, lineage stability, and full suppressive activity. Thus, those T cells in which the two events have concurrently occurred are developmentally set into the Treg cell lineage. This model explains how Treg cell fate and plasticity is controlled and can be exploited to generate functionally stable Treg cells.Citation
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. 2012, 37 (5):785-99 ImmunityAffiliation
Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.Journal
ImmunityPubMed ID
23123060Type
ArticleLanguage
enISSN
1097-4180ae974a485f413a2113503eed53cd6c53
10.1016/j.immuni.2012.09.010
Scopus Count
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