Epigenetic and transcriptional signatures of stable versus plastic differentiat...

• Author(s): Schmolka, Nina ; Serre, Karine ; Grosso, Ana R. ; Rei, Margarida ; Pennington, Daniel J. ; Gomes, Anita Q. ; Silva-Santos, Bruno
• Date: 2013
• Persistent ID: http://hdl.handle.net/10400.21/3768
• Origin: Repositório Científico do Instituto Politécnico de Lisboa
• Subject(s): Cell differentiation; Cytokines; Gene expression profiling; Gene expression regulation; Methylation; T-Lymphocyte subsets; Th1 cells; Th17 cells; Transcriptome
• Document Type: Article
• Language: English

Description

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment.