Mast cells condition dendritic cells to mediate allograft tolerance.
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.
Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03756, USA.
Victor C
VC
de Vries
Karina
K
Pino-Lagos
Elizabeth C
EC
Nowak
Kathy A
KA
Bennett
Carla
C
Oliva
Randolph J
RJ
Noelle
D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D006801:Humans; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D012867:Skin / Q000276:immunology*; D016038:Skin Transplantation; D023001:Transplantation Tolerance; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D014409:Tumor Necrosis Factor-alpha