Systematic name M475
Brief description Genes down-regulated in resting CD4 [GeneID=920] T cells: healthy versus systemic lupus erythrematosus (SLE).
Full description or abstract CD3-positive T cells were negatively isolated from 10 SLE patients and 9 healthy controls without SLE. All of the SLE samples and control samples were compared with one another to identify baseline differences in expression due to the disease. Next, T cell preparations from 4 of the control subjects were stimulated with either Nitric Oxide (NOC-18) 600 uM for 24hr or stimulated through CD3/CD28 for 24hr to determine which genes were responsive to these signaling mechanisms. Here, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in SLE T cells. Activation of mTOR was inducible by NO, a key trigger of MHP which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in SLE T cells and, in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 over-expression was also inversely correlated with diminished TCR? protein levels. Combined with follow up studies, these results suggest that activation of mTOR causes the loss of TCR? in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19201859   Authors: Fernandez DR,Telarico T,Bonilla E,Li Q,Banerjee S,Middleton FA,Phillips PE,Crow MK,Oess S,Muller-Esterl W,Perl A
Exact source GSE13887_2804_200_DN
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Organism Homo sapiens
Contributed by Jernej Godec (Dana-Farber Cancer Institute)
Source platform HUMAN_GENE_SYMBOL
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Version history 7.3: Moved to ImmuneSigDB sub-collection.

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