Mast Cells Condition Dendritic Cells to Mediate Allograft Tolerance

de Vries, VC; Pino-Lagos, K; Nowak, EC; Bennett, KA; Oliva, C; Noelle, RJ


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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Título según WOS: Mast Cells Condition Dendritic Cells to Mediate Allograft Tolerance
Título de la Revista: IMMUNITY
Volumen: 35
Número: 4
Editorial: Cell Press
Fecha de publicación: 2011
Página de inicio: 550
Página final: 561
Idioma: English


Notas: ISI