title: Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis.
abstract: Counter-balancing regulatory mechanisms, such as the induction of regulatory T cells (Treg), limit the effects of autoimmune attack in neuroinflammation. However, the role of dendritic cells (DCs) as the most powerful antigen-presenting cells, which are intriguing therapeutic targets in this context, is not fully understood. Here, we demonstrate that conditional ablation of DCs during the priming phase of myelin-specific T cells in experimental autoimmune encephalomyelitis (EAE) selectively aborts inducible Treg (iTreg) induction, whereas generation of T helper (Th)1/17 cells is unaltered. DCs facilitate iTreg induction by creating a milieu with high levels of interleukin (IL)-2 due to a strong proliferative response. In the absence of DCs, B220+B cells take over priming of Th17 cells in the place of antigen-presenting cells (APCs), but not the induction of iTreg, thus leading to unregulated, severe autoimmunity.
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Paterka
authors.affiliation: Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
authors.forename: Jan Oliver
authors.initials: JO
authors.lastname: Voss
authors.affiliation: Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Werr
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Reuter
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Sophia
authors.initials: S
authors.lastname: Franck
authors.affiliation: Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Leuenberger
authors.affiliation: Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
authors.forename: Josephine
authors.initials: J
authors.lastname: Herz
authors.affiliation: Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
authors.forename: Helena
authors.initials: H
authors.lastname: Radbruch
authors.affiliation: Institute for Immunology, Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bopp
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Siffrin
authors.affiliation: Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn(2)), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany. Electronic address: frauke.zipp@unimedizin-mainz.de.
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
mesh_terms: D000818:Animals; D015551:Autoimmunity; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D016207:Cytokines; D016212:Transforming Growth Factor beta
keywords: Dendritic cells; EAE; Immune regulation; Multiple sclerosis; Th17; Treg cells