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Changes in histone acetylation and methylation that are important for persistent but not transient expression of CCR4 in human CD4+ T cells.
- Source :
-
European journal of immunology [Eur J Immunol] 2010 Nov; Vol. 40 (11), pp. 3183-3197. Date of Electronic Publication: 2010 Oct 20. - Publication Year :
- 2010
-
Abstract
- Although regulation of CXCR3 and CCR4 is related to Th1 and Th2 differentiation, respectively, many CXCR3(+) and CCR4(+) cells do not express IFN-γ and/or IL-4, suggesting that the chemokine receptor genes might be inducible by mechanisms that are lineage-independent. We investigated the regulation of CXCR3 versus IFNG, and CCR4 versus IL4 in human CD4(+) T cells by analyzing modifications of histone H3. In naïve cord-blood cells, under nonpolarizing conditions not inducing IL4, CCR4 was induced to high levels without many of the activation-associated changes in promoter histone H3 found for both IL4 and CCR4 in Th2 cells. Importantly, CCR4 expression was stable in Th2 cells, but fell in nonpolarized cells after the cells were rested; this decline could be reversed by increasing histone acetylation using sodium butyrate. Patterns of histone H3 modifications in CXCR3(+) CCR4(-) and CXCR3(-) CCR4(+) CD4(+) T-cell subsets from adult blood matched those in cells cultured under polarizing conditions in vitro. Our data show that high-level lineage-independent induction of CCR4 can occur following T-cell activation without accessibility-associated changes in histone H3, but that without such changes expression is transient rather than persistent.<br /> (Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Acetylation drug effects
Butyrates pharmacology
Cells, Cultured
Gene Expression Regulation drug effects
Histones metabolism
Humans
Interleukin-4 immunology
Interleukin-4 metabolism
Lymphocyte Activation drug effects
Methylation drug effects
Receptors, CCR4 biosynthesis
Receptors, CXCR3 biosynthesis
Receptors, CXCR3 immunology
Th1 Cells immunology
Th1 Cells metabolism
Th2 Cells metabolism
Gene Expression Regulation immunology
Histones immunology
Lymphocyte Activation immunology
Receptors, CCR4 immunology
Th2 Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1521-4141
- Volume :
- 40
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- European journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 20963786
- Full Text :
- https://doi.org/10.1002/eji.201040443