Journal
IMMUNITY
Volume 35, Issue 4, Pages 550-561Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2011.09.012
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Funding
- National Institutes of Health (United States) [R01AT005382, AI048667]
- Wellcome Trust
- MRC Centre for Transplantation (United Kingdom)
- National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) at Guy's and St Thomas' NHS Foundation Trust and King's College London
- Agency of Science, Technology and Research (A*STAR, Singapore)
- National Multiple Sclerosis Society
- BECAS Chile
- Medical Research Council [G0802651, G0600698B] Funding Source: researchfish
- MRC [G0802651] Funding Source: UKRI
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Peripheral tolerance orchestrated by regulatory T cells, dendritic cells (DCs), and mast cells (MCs) has been studied in several models including skin allograft tolerance. We now define a role for MCs in controlling DC behavior (conditioning) to facilitate tolerance. Under tolerant conditions, we show that MCs mediated a marked increase in tumor necrosis factor (TNF alpha)-dependent accumulation of graft-derived DCs in the dLN compared to nontolerant conditions. This increase of DCs in the dLN is due to the local production of granulocyte macrophage colony-stimulating factor (GM-CSF) by MCs that induces a survival advantage of graft-derived DCs. DCs that migrated to the dLN from the tolerant allograft were tolerogenic; i.e., they dominantly suppress T cell responses and control regional immunity. This study underscores the importance of MCs in conditioning DCs to mediate peripheral tolerance and shows a functional impact of peripherally produced TNF alpha and GM-CSF on the migration and function of tolerogenic DCs.
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