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Series GSE3337

Query DataSets for GSE3337

Status

Public on Dec 09, 2005

Title

Gene expression profiling of IDO-competent dendritic cells

Organism

Mus musculus

Experiment type

Expression profiling by array

Summary

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.
Keywords: Time-course, treatment with agent (IFN-gamma)

Overall design

Labeled cRNA extracted from a a total of 8 samples was hybridized to the Affymetrix GeneChip MG-U74Av2 which contains 12,488 probe sets . The 4 control samples included 2 replicates each of RNA extracted from cells incubated in medium for 4 and 16 hours. Treated samples included 2 replicates each of RNA extracted from cells incubated in IFN-gammas for 4 and 16 hours.

Contributor(s)

Grohmann U, Orabona C, Luchini A, Bicciato S

Citation(s)

16339401

Submission date

Sep 21, 2005

Last update date

Feb 18, 2018

Contact name

Silvio Bicciato

E-mail(s)

[email protected]