Human Gene Set: GSE11884_WT_VS_FURIN_KO_NAIVE_CD4_TCELL_DN


Standard name GSE11884_WT_VS_FURIN_KO_NAIVE_CD4_TCELL_DN
Systematic name M410
Brief description Genes down-regulated in naïve wildtype CD4 [GeneID=920] T cells versus those from T cell specific FURIN [GeneID=5045] knockout mice.
Full description or abstract Furin is a proprotein convertase induced in activated T cells, reported to processes the anti-inflammatory cytokine TGFb-1. Herein, we show that conditional deletion of furin in T cells allowed for normal T cell development but impaired the function of regulatory T cells and effector cells, which produced less TGFb-1. Furin-deficient Treg cells, were less protective in a T cell transfer colitis model and failed to induce Foxp3 in normal T cells. Furin-deficient effector cells were inherently overly active and were resistant to suppressive activity of wild-type Tregs. Thus, our results indicate that furin is indispensable in maintaining peripheral tolerance, which is due, at least in part, to its nonredundant, essential function in regulating TGFb-1 production. Targeting furin has emerged as a strategy in malignant and infectious disease. The current work suggests that inhibiting furin might activate immune responses, but may result in a breakdown in peripheral tolerance.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 18701887   Authors: Pesu M,Watford WT,Wei L,Xu L,Fuss I,Strober W,Andersson J,Shevach EM,Quezado M,Bouladoux N,Roebroek A,Belkaid Y,Creemers J,O'Shea JJ
Exact source GSE11884_2701_200_DN
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Source species Mus musculus
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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