NDLI: In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

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In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

Content Provider	PubMed Central
Author	Ioannou, Marianna Alissafi, Themis Boon, Louis Dimitrios, Boumpas Verginis, Panayotis
Copyright Year	2013
Abstract	Autoimmunity ensues upon breakdown of tolerance mechanism and priming of self-reactive T cells. Plasmacytoid dendritic cells (pDCs) constitute a unique cell subset that participates in the activation of autoreactive T cells but also has been shown to be critically involved in the induction of self-tolerance. However, their functional importance during the priming phase of an organ-specific autoimmune response remains unclear. In this study, we demonstrate that absence of pDCs during myelin antigenic challenge resulted in amelioration of experimental autoimmune encephalomyelitis and reduced disease severity. This was accompanied by significantly decreased frequency of myelin-specific T cells in the draining lymph nodes and inhibition of Th1 and Th17 immune responses. Unexpectedly, in vivo ablation of pDCs increased myelopoiesis in the bone marrow and specifically induced the generation of CD11bhiGr1+ myeloid-derived suppressor cells (MDSCs). Furthermore, we demonstrate that pDC depletion enhanced the mobilization of MDSCs in the spleen, and that sorted MDSCs could potently suppress CD4+ T cell responses in vitro. Importantly, pDC-depleted mice showed increased levels of MCP-1 in the draining lymph nodes, and in vivo administration of MCP-1 increased the frequency and absolute numbers of MDSCs in the periphery of treated mice. Together, our results reveal that absence of pDCs during the priming of an autoimmune response leads to increased mobilization of MDSCs in the periphery in an MCP-1–dependent manner and subsequent amelioration of autoimmunity.
Related Links	http://dx.doi.org/10.4049/jimmunol.1201897
Ending Page	2640
Page Count	10
Starting Page	2631
File Format	PDF
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology Author Choice
Issue Number	6
Volume Number	190
Language	English
Publisher	AAI
Publisher Date	2013-03-15
Access Restriction	Open
Rights Holder	AAI
Subject Keyword	Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Correction: In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

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In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

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Correction: In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells

In vivo ablation of plasmacytoid dendritic cells inhibits autoimmunity through expansion of myeloid-derived suppressor cells.

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In Vivo Ablation of Plasmacytoid Dendritic Cells Inhibits Autoimmunity through Expansion of Myeloid-Derived Suppressor Cells