학술논문
Dendritic Cells Ameliorate Autoimmunity in the CNS by Controlling the Homeostasis of PD-1 Receptor+ Regulatory T Cells
Document Type
Article
Author
Yogev, Nir; Frommer, Friederike; Lukas, Dominika; Kautz-Neu, Kordula; Karram, Khalad; Ielo, Daniele; von Stebut, Esther; Probst, Hans-Christian; van den Broek, Maries; Riethmacher, Dieter; Birnberg, Tal; Blank, Thomas; Reizis, Boris; Korn, Thomas; Wiendl, Heinz; Jung, Steffen; Prinz, Marco; Kurschus, Florian C.; Waisman, Ari
Source
Subject
*DENDRITIC cells
*AUTOIMMUNITY
*CENTRAL nervous system
*HOMEOSTASIS
*T cells
*ANTIGENS
*ANTIGEN presenting cells
*IMMUNE response
*
*
*
*
*
*
*
Language
ISSN
1074-7613
Abstract
Summary: 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. [ABSTRACT FROM AUTHOR]