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J Autoimmun. 2017 Jan;76:108-114. doi: 10.1016/j.jaut.2016.09.008. Epub 2016 Oct 2.

Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis.

Author information

1
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.
2
Molecular Neurology, Max Delbrück Center for Molecular Medicine Berlin-Buch, Berlin, Germany.
3
Institute for Immunology, Research Center for Immunotherapy (FZI), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
4
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.

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.

KEYWORDS:

Dendritic cells; EAE; Immune regulation; Multiple sclerosis; Th17; Treg cells

PMID:
27707650
DOI:
10.1016/j.jaut.2016.09.008
[Indexed for MEDLINE]

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