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Nucleic Acids Res. 2015 Feb 18;43(3):1537-48. doi: 10.1093/nar/gkv014. Epub 2015 Jan 15.

Development of a unique epigenetic signature during in vivo Th17 differentiation.

Author information

1
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
2
Institute for Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
3
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany jochen.huehn@helmholtz-hzi.de.

Abstract

Activated naive CD4(+) T cells are highly plastic cells that can differentiate into various T helper (Th) cell fates characterized by the expression of effector cytokines like IFN-γ (Th1), IL-4 (Th2) or IL-17A (Th17). Although previous studies have demonstrated that epigenetic mechanisms including DNA demethylation can stabilize effector cytokine expression, a comprehensive analysis of the changes in the DNA methylation pattern during differentiation of naive T cells into Th cell subsets is lacking. Hence, we here performed a genome-wide methylome analysis of ex vivo isolated naive CD4(+) T cells, Th1 and Th17 cells. We could demonstrate that naive CD4(+) T cells share more demethylated regions with Th17 cells when compared to Th1 cells, and that overall Th17 cells display the highest number of demethylated regions, findings which are in line with the previously reported plasticity of Th17 cells. We could identify seven regions located in Il17a, Zfp362, Ccr6, Acsbg1, Dpp4, Rora and Dclk1 showing pronounced demethylation selectively in ex vivo isolated Th17 cells when compared to other ex vivo isolated Th cell subsets and in vitro generated Th17 cells, suggesting that this unique epigenetic signature allows identifying and functionally characterizing in vivo generated Th17 cells.

PMID:
25593324
PMCID:
PMC4330377
DOI:
10.1093/nar/gkv014
[Indexed for MEDLINE]
Free PMC Article

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