Dendritic cells tip the balance towards induction of regulatory T cells upon priming in experimental autoimmune encephalomyelitis. (January 2017)

• Record Type: Journal Article
• Authors: Paterka, Magdalena; Voss, Jan Oliver; Werr, Johannes; Reuter, Eva; Franck, Sophia; Leuenberger, Tina; Herz, Josephine; Radbruch, Helena; Bopp, Tobias; Siffrin, Volker; Zipp, Frauke
• Is Part Of: Journal of autoimmunity. Volume 76(2017)
• Page Start: 108
• Page End: 114
• Publication Date: 2017-01
• Subjects: EAE -- Dendritic cells -- Immune regulation -- Th17 -- Treg cells -- Multiple sclerosis; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; Autoantibodies -- Periodicals; Autoimmune Diseases -- Periodicals; Auto-immunité -- Périodiques; Maladies auto-immunes -- Périodiques; Electronic journals; 616.978005
• DOI: 10.1016/j.jaut.2016.09.008
• Languages: English
• ISSNs: 0896-8411

Abstract

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. Highlights: Dendritic cells are potential therapeutic targets in autoimmune neuroinflammation. Studied with transgenic mice and experimental autoimmune encephalomyelitis (EAE). Conditional ablation of DCs during disease initiation leads to exacerbated EAE course. No increase in regulatory T cells (Treg) in secondary lymphoid organs and CNS. Evidence for a protective role of DCs in the initiating phase of EAE.