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

      Yang, Bi-Huei; Floess, Stefan; Hagemann, Stefanie; Deyneko, Igor V; Groebe, Lothar; Pezoldt, Joern; Sparwasser, Tim; Lochner, Matthias; Huehn, Jochen; Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany. (2015-02-18)
      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.
    • Impact of CCR7 on T-Cell Response and Susceptibility to Yersinia pseudotuberculosis Infection.

      Pezoldt, Joern; Pisano, Fabio; Heine, Wiebke; Pasztoi, Maria; Rosenheinrich, Maik; Nuss, Aaron M; Pils, Marina C; Prinz, Immo; Förster, Reinhold; Huehn, Jochen; et al. (2017-09-15)
      To successfully limit pathogen dissemination, an immunological link between the entry tissue of the pathogen and the underlying secondary lymphoid organs (SLOs) needs to be established to prime adaptive immune responses. Here, the prerequisite of CCR7 to mount host immune responses within SLOs during gastrointestinal Yersinia pseudotuberculosis infection to limit pathogen spread was investigated.