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The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation
Abstract
T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8+ T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8+ T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Upon secondary recall, TET2-deficient memory CD8+ T cells demonstrate superior pathogen control. Genome-wide methylation analysis identified a number of differentially methylated regions in TET2-deficient versus wild-type CD8+ T cells. These differentially methylated regions did not occur at the loci of differentially expressed memory markers; rather, several hypermethylated regions were identified in known transcriptional regulators of CD8+ T cell memory fate. Together, these data demonstrate that TET2 is an important regulator of CD8+ T cell fate decisions.
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“In this context, IL-17A production by T helper 17 (T H 17) cells, group 3 innate lymphoid cells (ILC3s) and inflammatory group 2 innate lymphoid cells (iILC2s) is significantly reduced in the setting of TET2 deficiency162,172.”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [162]
In the citing paper
“InmouseCD4+Tcellsand innate lymphoid cell (ILC) subsets, TET2 is recruited to the Il17a enhancer CNS2 via RORγt, leading to increased enhancer and promoter hydroxymethylation and increased Il17a expression162.”
From Clonal haematopoiesis and dysregulation of the immune system (2023) · cites this paper as [162]
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Metadata
- Authors
- Carty, S. A., Gohil, M., Banks, L. B., Cotton, R. M., Johnson, M. E., Stelekati, E., Wells, A. D., Wherry, E. J., Koretzky, G. A., & Jordan, M. S.
- Affiliations
- Department of Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
- Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
- The Children’s Hospital of Philadelphia , Philadelphia, PA 19104
- Department of Microbiology, Perelman School of Medicine, University of Pennsylvania , Philadelphia, PA 19104
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2018-01-01
- Volume
- 200
- Issue
- 1
- Pages
- 82-91
- ISSN
- 0022-1767
- 1550-6606
- PMC
- PMC5736442
- Cited by
- 172
- References
- 74
- Language
- en
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