Epigenetic control of CD8+ T cell differentiation
Key Points According to the linear differentiation model, progressive changes to gene expression and the epigenetic landscape regulate the gradual acquisition of effector function and restriction of differentiation potential that occur during CD8 + T cell differentiation. DNA methylation, histone mo...
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| Veröffentlicht in: | Nature reviews. Immunology Jg. 18; H. 5; S. 340 - 356 |
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| Hauptverfasser: | , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
London
Nature Publishing Group UK
01.05.2018
Nature Publishing Group |
| Schlagworte: | |
| ISSN: | 1474-1733, 1474-1741, 1474-1741 |
| Online-Zugang: | Volltext |
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| Zusammenfassung: | Key Points
According to the linear differentiation model, progressive changes to gene expression and the epigenetic landscape regulate the gradual acquisition of effector function and restriction of differentiation potential that occur during CD8
+
T cell differentiation.
DNA methylation, histone modification and chromatin architecture are major epigenetic mechanisms that regulate CD8
+
T cell differentiation and function, allowing for signal-driven establishment and heritable maintenance of transcriptional changes.
Epigenetic modifying proteins can act differentially within CD8
+
T cell differentiation subsets to regulate gene expression, and altering the activities of these enzymes can have profound effects on T cell differentiation and function.
T cell exhaustion represents a state of arrested differentiation. Reversal of T cell exhaustion liberates effector function but may negatively impact the persistence of antigen-specific T cells.
Increasing our understanding of the epigenetics underlying CD8
+
T cell differentiation may enable a greater understanding of T cell biology and its enormous therapeutic possibilities.
CD8
+
T cell differentiation and function are regulated by epigenetic changes mainly including DNA methylation, histone modification and modification of chromatin architecture. As described here, a detailed understanding of these epigenetic mechanisms can be harnessed to improve T cell-based immunotherapies.
Upon stimulation, small numbers of naive CD8
+
T cells proliferate and differentiate into a variety of memory and effector cell types. CD8
+
T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8
+
T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8
+
T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements. We also describe structural changes in chromatin organization that affect gene expression. Finally, we examine the translational potential of epigenetic interventions to improve CD8
+
T cell function in individuals with chronic infections and cancer. |
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| Bibliographie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 A.N.H. researched data for the article. A.N.H. and R.R. made substantial contributions to discussion of the content, wrote the article and reviewed and edited the manuscript before submission. N.P.R. contributed to discussion of the content and reviewed and edited the manuscript before submission. Author contributions |
| ISSN: | 1474-1733 1474-1741 1474-1741 |
| DOI: | 10.1038/nri.2017.146 |