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dc.contributor.authorHerppich, Susanne
dc.contributor.authorToker, Aras
dc.contributor.authorPietzsch, Beate
dc.contributor.authorKitagawa, Yohko
dc.contributor.authorOhkura, Naganari
dc.contributor.authorMiyao, Takahisa
dc.contributor.authorFloess, Stefan
dc.contributor.authorHori, Shohei
dc.contributor.authorSakaguchi, Shimon
dc.contributor.authorHuehn, Jochen
dc.date.accessioned2019-11-26T14:32:23Z
dc.date.available2019-11-26T14:32:23Z
dc.date.issued2019-01-01
dc.identifier.citationFront Immunol. 2019 Oct 11;10:2382. doi: 10.3389/fimmu.2019.02382. eCollection 2019.en_US
dc.identifier.issn1664-3224
dc.identifier.pmid31681278
dc.identifier.doi10.3389/fimmu.2019.02382
dc.identifier.urihttp://hdl.handle.net/10033/622031
dc.description.abstractRegulatory T (Treg) cells mainly develop within the thymus and arise from CD25+Foxp3- (CD25+ TregP) or CD25-Foxp3+ (Foxp3+ TregP) Treg cell precursors resulting in Treg cells harboring distinct transcriptomic profiles and complementary T cell receptor repertoires. The stable and long-term expression of Foxp3 in Treg cells and their stable suppressive phenotype are controlled by the demethylation of Treg cell-specific epigenetic signature genes including an evolutionarily conserved CpG-rich element within the Foxp3 locus, the Treg-specific demethylated region (TSDR). Here we analyzed the dynamics of the imprinting of the Treg cell-specific epigenetic signature genes in thymic Treg cells. We could demonstrate that CD25+Foxp3+ Treg cells show a progressive demethylation of most signature genes during maturation within the thymus. Interestingly, a partial demethylation of several Treg cell-specific epigenetic signature genes was already observed in Foxp3+ TregP but not in CD25+ TregP. Furthermore, Foxp3+ TregP were very transient in nature and arose at a more mature developmental stage when compared to CD25+ TregP. When the two Treg cell precursors were cultured in presence of IL-2, a factor known to be critical for thymic Treg cell development, we observed a major impact of IL-2 on the demethylation of the TSDR with a more pronounced effect on Foxp3+ TregP. Together, these results suggest that the establishment of the Treg cell-specific hypomethylation pattern is a continuous process throughout thymic Treg cell development and that the two known Treg cell precursors display distinct dynamics for the imprinting of the Treg cell-specific epigenetic signature genes.en_US
dc.language.isoenen_US
dc.publisherFrontiersen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectFoxp3en_US
dc.subjectIL-2en_US
dc.subjectTSDRen_US
dc.subjectTreg cellen_US
dc.subjectTreg cell precursorsen_US
dc.subjectdemethylationen_US
dc.subjectepigenetic signatureen_US
dc.subjectthymusen_US
dc.titleDynamic Imprinting of the Treg Cell-Specific Epigenetic Signature in Developing Thymic Regulatory T Cells.en_US
dc.typeArticleen_US
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalFrontiers in Immunologyen_US
refterms.dateFOA2019-11-26T14:32:23Z
dc.source.journaltitleFrontiers in immunology


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