Mast Cells Condition Dendritic Cells to Mediate Allograft Tolerance

Victor C. de Vries, Karina Pino-Lagos, Elizabeth C. Nowak, Kathy A. Bennett, Carla Oliva, Randolph J. Noelle

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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 (TNFα)-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 TNFα and GM-CSF on the migration and function of tolerogenic DCs.
Original languageAmerican English
Pages (from-to)550-561
Number of pages12
JournalImmunity
Volume35
Issue number4
DOIs
StatePublished - 28 Oct 2011
Externally publishedYes

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