T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.

2.50
Hdl Handle:
http://hdl.handle.net/10033/268892
Title:
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
Authors:
Ohkura, Naganari; Hamaguchi, 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
Abstract:
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.
Affiliation:
Department of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.
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 Immunity
Journal:
Immunity
Issue Date:
16-Nov-2012
URI:
http://hdl.handle.net/10033/268892
DOI:
10.1016/j.immuni.2012.09.010
PubMed ID:
23123060
Type:
Article
Language:
en
ISSN:
1097-4180
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorOhkura, Naganarien_GB
dc.contributor.authorHamaguchi, Masahideen_GB
dc.contributor.authorMorikawa, Hiromasaen_GB
dc.contributor.authorSugimura, Kyokoen_GB
dc.contributor.authorTanaka, Atsushien_GB
dc.contributor.authorIto, Yoshinagaen_GB
dc.contributor.authorOsaki, Motonaoen_GB
dc.contributor.authorTanaka, Yoshiakien_GB
dc.contributor.authorYamashita, Riuen_GB
dc.contributor.authorNakano, Naokoen_GB
dc.contributor.authorHuehn, Jochenen_GB
dc.contributor.authorFehling, Hans Joergen_GB
dc.contributor.authorSparwasser, Timen_GB
dc.contributor.authorNakai, Kentaen_GB
dc.contributor.authorSakaguchi, Shimonen_GB
dc.date.accessioned2013-02-11T10:31:47Z-
dc.date.available2013-02-11T10:31:47Z-
dc.date.issued2012-11-16-
dc.identifier.citationT cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development. 2012, 37 (5):785-99 Immunityen_GB
dc.identifier.issn1097-4180-
dc.identifier.pmid23123060-
dc.identifier.doi10.1016/j.immuni.2012.09.010-
dc.identifier.urihttp://hdl.handle.net/10033/268892-
dc.description.abstractThe 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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Immunityen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshDNA Methylationen_GB
dc.subject.meshEpigenesis, Geneticen_GB
dc.subject.meshForkhead Transcription Factorsen_GB
dc.subject.meshGene Expressionen_GB
dc.subject.meshHistonesen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMice, Inbred BALB Cen_GB
dc.subject.meshMice, Inbred C57BLen_GB
dc.subject.meshReceptors, Antigen, T-Cellen_GB
dc.subject.meshT-Lymphocytes, Regulatoryen_GB
dc.subject.meshThymus Glanden_GB
dc.titleT cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.en
dc.typeArticleen
dc.contributor.departmentDepartment of Experimental Immunology, World Premier International Immunology Frontier Research Center, Osaka University, Suita, Japan.en_GB
dc.identifier.journalImmunityen_GB

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