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

Authors

  • M. Paterka
  • J.O. Voss
  • J. Werr
  • E. Reuter
  • S. Franck
  • T. Leuenberger
  • J. Herz
  • H. Radbruch
  • T. Bopp
  • V. Siffrin
  • F. Zipp

Journal

  • Journal of Autoimmunity

Citation

  • J Autoimmun 76: 108-114

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.


DOI

doi:10.1016/j.jaut.2016.09.008