Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells.

Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany. yogev@uni-mainz.de

Immunity 2012 Aug 24

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Mature dendritic cells (DCs) are established as unrivaled antigen-presenting cells (APCs) in the initiation of immune responses, whereas steady-state DCs induce peripheral T cell tolerance. Using various genetic approaches, we depleted CD11c(+) DCs in mice and induced autoimmune CNS inflammation. Unexpectedly, mice lacking DCs developed aggravated disease compared to control mice. Furthermore, when we engineered DCs to present a CNS-associated autoantigen in an induced manner, we found robust tolerance that prevented disease, which coincided with an upregulation of the PD-1 receptor on antigen-specific T cells. Additionally, we showed that PD-1 was necessary for DC-mediated induction of regulatory T cells. Our results show that a reduction of DCs interferes with tolerance, resulting in a stronger inflammatory response, and that other APC populations could compensate for the loss of immunogenic APC function in DC-depleted mice. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Nir Yogev, Friederike Frommer, Dominika Lukas, Kordula Kautz-Neu, Khalad Karram, Daniele Ielo, Esther von Stebut, Hans-Christian Probst, Maries van den Broek, Dieter Riethmacher, Tal Birnberg, Thomas Blank, Boris Reizis, Thomas Korn, Heinz Wiendl, Steffen Jung, Marco Prinz, Florian C Kurschus, Ari Waisman. Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells. Immunity. 2012 Aug 24;37(2):264-75