Title: T-cell-expressed proprotein convertase furin is essential for maintenance of peripheral immune tolerance
Authors: Pesu, Marko ×
Watford, Wendy T
Wei, Lai
Xu, Lili
Fuss, Ivan
Strober, Warren
Andersson, John
Shevach, Ethan M
Quezado, Martha
Bouladoux, Nicolas
Roebroek, Anton
Belkaid, Yasmine
Creemers, John
O'Shea, John J #
Issue Date: Sep-2008
Publisher: Nature publishing group
Series Title: Nature vol:455 issue:7210 pages:246-250
Abstract: Furin is one of seven proprotein convertase family members that promote proteolytic maturation of proproteins(1). It is induced in activated T cells and is reported to process a variety of substrates including the anti- inflammatory cytokine transforming growth factor (TGF)-beta 1 ( refs 2 - 4), but the non- redundant functions of furin versus other proprotein convertases in T cells are unclear. Here we show that conditional deletion of furin in T cells allowed for normal T- cell development but impaired the function of regulatory and effector T cells, which produced less TGF-beta 1. Furin-deficient T regulatory (T-reg) cells were less protective in a T- cell transfer colitis model and failed to induce Foxp3 in normal T cells. Additionally, furin- deficient effector cells were inherently over-active and were resistant to suppressive activity of wild- type T-reg cells. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its non- redundant, essential function in regulating TGF-beta 1 production. Targeting furin has emerged as a strategy in malignant and infectious disease(5,6). Our results suggest that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
ISSN: 0028-0836
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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