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Dynamic Imprinting of the Treg Cell-Specific Epigenetic Signature in Developing Thymic Regulatory T Cells.
- Source :
-
Frontiers in immunology [Front Immunol] 2019 Oct 11; Vol. 10, pp. 2382. Date of Electronic Publication: 2019 Oct 11 (Print Publication: 2019). - Publication Year :
- 2019
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Abstract
- Regulatory T (Treg) cells mainly develop within the thymus and arise from CD25 <superscript>+</superscript> Foxp3 <superscript>-</superscript> (CD25 <superscript>+</superscript> TregP) or CD25 <superscript>-</superscript> Foxp3 <superscript>+</superscript> (Foxp3 <superscript>+</superscript> 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 <superscript>+</superscript> Foxp3 <superscript>+</superscript> 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 <superscript>+</superscript> TregP but not in CD25 <superscript>+</superscript> TregP. Furthermore, Foxp3 <superscript>+</superscript> TregP were very transient in nature and arose at a more mature developmental stage when compared to CD25 <superscript>+</superscript> 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 <superscript>+</superscript> 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.<br /> (Copyright © 2019 Herppich, Toker, Pietzsch, Kitagawa, Ohkura, Miyao, Floess, Hori, Sakaguchi and Huehn.)
- Subjects :
- Animals
Forkhead Transcription Factors genetics
Forkhead Transcription Factors immunology
Mice
Mice, Transgenic
T-Lymphocytes, Regulatory cytology
Thymocytes cytology
Thymus Gland cytology
DNA Methylation genetics
DNA Methylation immunology
Genetic Loci immunology
Genomic Imprinting immunology
T-Lymphocytes, Regulatory immunology
Thymocytes immunology
Thymus Gland immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1664-3224
- Volume :
- 10
- Database :
- MEDLINE
- Journal :
- Frontiers in immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31681278
- Full Text :
- https://doi.org/10.3389/fimmu.2019.02382