In:
The Journal of Immunology, The American Association of Immunologists, Vol. 194, No. 12 ( 2015-06-15), p. 5812-5824
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.
Type of Medium:
Online Resource
ISSN:
0022-1767
,
1550-6606
DOI:
10.4049/jimmunol.1500111
Language:
English
Publisher:
The American Association of Immunologists
Publication Date:
2015
detail.hit.zdb_id:
1475085-5