Format

Send to

Choose Destination
J Immunol. 2015 Jun 15;194(12):5812-24. doi: 10.4049/jimmunol.1500111. Epub 2015 May 6.

De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.

Author information

1
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 71300 Heraklion, Greece; Laboratory of Autoimmunity and Inflammation, University of Crete Medical School, 71300 Heraklion, Greece; Division of Clinical, Experimental Surgery, & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece;
2
Division of Clinical, Experimental Surgery, & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece;
3
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, 71300 Heraklion, Greece;
4
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, 30625 Hannover, Germany; and.
5
Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, 10117 Berlin, Germany.
6
Division of Clinical, Experimental Surgery, & Translational Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece; pverginis@bioacademy.gr.

Abstract

Foxp3(+) regulatory T cell (Treg)-based immunotherapy holds promise for autoimmune diseases. However, this effort has been hampered by major caveats, including the low frequency of autoantigen-specific Foxp3(+) Tregs and lack of understanding of their molecular and cellular targets, in an unmanipulated wild-type (WT) immune repertoire. In this study, we demonstrate that infusion of myelin in WT mice results in the de novo induction of myelin-specific Foxp3(+) Tregs in WT mice and amelioration of experimental autoimmune encephalomyelitis. Myelin-specific Foxp3(+) Tregs exerted their effect both by diminishing Ag-bearing inflammatory dendritic cell (iDC) recruitment to lymph nodes and by impairing their function. Transcriptome analysis of ex vivo-isolated Treg-exposed iDCs showed significant enrichment of transcripts involved in functional properties of iDCs, including chemotaxis-related genes. To this end, CCR7 expression by iDCs was significantly downregulated in tolerant mice and this was tightly regulated by the presence of IL-10. Collectively, our data demonstrate a novel model for deciphering the Ag-specific Foxp3(+) Treg-mediated mechanisms of tolerance and delineate iDCs as a Foxp3(+) Treg cellular target in unmanipulated mice.

PMID:
25948818
DOI:
10.4049/jimmunol.1500111
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center