1. Dendritic cells ameliorate autoimmunity in the CNS by controlling the homeostasis of PD-1 receptor(+) regulatory T cells.
- Author
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Yogev N, Frommer F, Lukas D, Kautz-Neu K, Karram K, Ielo D, von Stebut E, Probst HC, van den Broek M, Riethmacher D, Birnberg T, Blank T, Reizis B, Korn T, Wiendl H, Jung S, Prinz M, Kurschus FC, and Waisman A
- Subjects
- Animals, Antigen Presentation immunology, Autoantigens immunology, Autoimmunity immunology, B7-H1 Antigen immunology, B7-H1 Antigen metabolism, CD11c Antigen, Dendritic Cells metabolism, Mice, Mice, Inbred C57BL, Mice, Knockout, Programmed Cell Death 1 Receptor metabolism, T-Lymphocytes, Regulatory metabolism, Th1 Cells immunology, Th1 Cells metabolism, Th17 Cells immunology, Th17 Cells metabolism, Dendritic Cells immunology, Encephalomyelitis, Autoimmune, Experimental immunology, Immune Tolerance immunology, Programmed Cell Death 1 Receptor immunology, T-Lymphocytes, Regulatory immunology
- Abstract
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.)
- Published
- 2012
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