Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+thymocyte stage

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http://hdl.handle.net/10138/309634

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Vanhanen , R , Leskinen , K , Mattila , I P , Saavalainen , P & Arstila , T P 2020 , ' Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+thymocyte stage ' , Cellular Immunology , vol. 347 , 104026 . https://doi.org/10.1016/j.cellimm.2019.104026

Title: Epigenetic and transcriptional analysis supports human regulatory T cell commitment at the CD4+CD8+thymocyte stage
Author: Vanhanen, Reetta; Leskinen, Katarzyna; Mattila, Ilkka P.; Saavalainen, Päivi; Arstila, T. Petteri
Contributor: University of Helsinki, Faculty of Medicine
University of Helsinki, TRIMM - Translational Immunology Research Program
University of Helsinki, HUS Children and Adolescents
University of Helsinki, Doctoral Programme in Biomedicine
University of Helsinki, Research Programs Unit
Date: 2020-01
Language: eng
Number of pages: 7
Belongs to series: Cellular Immunology
ISSN: 0008-8749
URI: http://hdl.handle.net/10138/309634
Abstract: The natural CD25 + FOXP3 + regulatory T cell (Treg) population is generated as a distinct lineage in the thymus, but the details of Treg development in humans remain unclear, and the timing of Treg commitment is also contested. Here we have analyzed the emergence of CD25 + cells at the CD4 + CD8 + double positive (DP) stage in the human thymus. We show that these cells share T cell receptor repertoire with CD25 + CD4 single-positive thymocytes, believed to be committed Tregs. They already have a fully demethylated FOXP3 enhancer region and thus display stable expression of FOXP3 and the associated Treg phenotype. Transcriptome analysis also grouped the DP CD25 + and CD4 CD25 + thymocytes apart from the CD25 - subsets. Together with earlier studies, our data are consistent with human Treg commitment already at the DP thymocyte stage. We suggest that the most important antigens and signals necessary for human Treg differentiation may be found in the thymic cortex.
Subject: FOXP3
Regulatory T cells
TCR
Thymus
FOXP3 LOCUS
THYMOCYTES
CD4(+)CD8(+)
SELECTION
INTERLEUKIN-2
DEMETHYLATION
ACTIVATION
EXPRESSION
ABSENCE
AND-15
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
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