Human Gene Set: GSE3337_4H_VS_16H_IFNG_IN_CD8POS_DC_DN

Standard name GSE3337_4H_VS_16H_IFNG_IN_CD8POS_DC_DN
Systematic name M5104
Brief description Genes down-regulated in comparison of untreated CD8+ dendritic cells (DC) at 4 h versus those treated with IFNG [GeneID=3458] at 16 h.
Full description or abstract Although much is known on the transcriptional profiles of dendritic cells (DCs) during maturation, the molecular switches critical for the acquisition of a tolerogenic program by DCs are still obscure. In the present study, we explored the gene expression pattern of CD8+ DCs purified from the mouse spleen and treated with interferon (IFN)-gamma. The cytokine, indeed, potentiates the tolerogenic potential of this DC subset via induction of the immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO). By comparing the expression of the IFN-gamma-modulated genes in IDO+ versus IDO- murine DCs, we found a consistent and selective association of the IDO-competent phenotype with the down-modulation of the Tyrobp gene, encoding the adapter molecule DAP12. IFN-gamma-mediated down-modulation of this gene involved IFN consensus sequence binding protein (ICSBP), a transcription factor also known as IRF-8. While silencing of Tyrobp conferred IDO functional competence on IDO- DCs, silencing of Icsbp1 in IDO+ cells completely abolished IDO expression and function. In parallel, silencing of TYROBP conferred IDO competence on human IDO- DCs while silencing of IRF8 impaired IDO expression and activity in human IDO+ DCs. Therefore, the same small set of molecular switches controls IDO competence in murine and human DCs.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 16339401   Authors: Orabona C,Puccetti P,Vacca C,Bicciato S,Luchini A,Fallarino F,Bianchi R,Velardi E,Perruccio K,Velardi A,Bronte V,Fioretti MC,Grohmann U
Exact source GSE3337_1055_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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