title: Development of a unique epigenetic signature during in vivo Th17 differentiation.
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.
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Bi-Huei
authors.initials: BH
authors.lastname: Yang
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Floess
authors.affiliation: 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.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Hagemann
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Igor V
authors.initials: IV
authors.lastname: Deyneko
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Groebe
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
authors.forename: Joern
authors.initials: J
authors.lastname: Pezoldt
authors.affiliation: 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.
authors.forename: Tim
authors.initials: T
authors.lastname: Sparwasser
authors.affiliation: 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.
authors.forename: Matthias
authors.initials: M
authors.lastname: Lochner
authors.affiliation: Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany jochen.huehn@helmholtz-hzi.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Huehn
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D058504:Th17 Cells / Q000166:cytology*