Dendritic Cells Ameliorate Autoimmunity in the CNS by Controlling the Homeostasis of PD-1 Receptor⁺ Regulatory T Cells

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• 作者：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
• 刊名：Immunity
• 出版年：2012
• 出版时间：24 August, 2012
• 年：2012
• 卷：37
• 期：2
• 页码：264-275
• 全文大小：5343 K

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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.