Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.
In: Journal of Clinical Investigation, Jg. 130 (2020-12-01), Heft 12, S. 1-19
academicJournal
Zugriff:
Tregs require Foxp3 expression and induction of a specific DNA hypomethylation signature during development, after which Tregs persist as a self-renewing population that regulates immune system activation. Whether maintenance DNA methylation is required for Treg lineage development and stability and how methylation patterns are maintained during lineage self-renewal remain unclear. Here, we demonstrate that the epigenetic regulator ubiquitin-like with plant homeodomain and RING finger domains 1 (Uhrf1) is essential for maintenance of methyl-DNA marks that stabilize Treg cellular identity by repressing effector T cell transcriptional programs. Constitutive and induced deficiency of Uhrf1 within Foxp3+ cells resulted in global yet nonuniform loss of DNA methylation, derepression of inflammatory transcriptional programs, destabilization of the Treg lineage, and spontaneous inflammation. These findings support a paradigm in which maintenance DNA methylation is required in distinct regions of the Treg genome for both lineage establishment and stability of identity and suppressive function. [ABSTRACT FROM AUTHOR]
Titel: |
Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.
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Autor/in / Beteiligte Person: | Helmin, Kathryn A. ; Morales-Nebreda, Luisa ; Torres Acosta, Manuel A. ; Anekalla, Kishore R. ; Chen, Shang-Yang ; Abdala-Valencia, Hiam ; Politanska, Yuliya ; Cheresh, Paul ; Akbarpour, Mahzad ; Steinert, Elizabeth M. ; Weinberg, Samuel E. ; Singer, Benjamin D. ; Acosta, Manuel A Torres |
Zeitschrift: | Journal of Clinical Investigation, Jg. 130 (2020-12-01), Heft 12, S. 1-19 |
Veröffentlichung: | 2020 |
Medientyp: | academicJournal |
ISSN: | 0021-9738 (print) |
DOI: | 10.1172/JCI137712 |
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