Human Gene Set: GSE14350_TREG_VS_TEFF_IN_IL2RB_KO_DN


Standard name GSE14350_TREG_VS_TEFF_IN_IL2RB_KO_DN
Systematic name M3420
Brief description Genes down-regulated in comparison of regulatory T cell (Treg) from IL2RB [GeneID=3560] defficient mice versus effector T cells from IL2RB [GeneID=3560] defficient mice.
Full description or abstract Interleukin-2 receptor (IL-2R) signaling is essential for T regulatory (Treg) cell development and homeostasis. Here we show that expression of IL-2Rbeta chains that lack tyrosine residues important for the association of the adaptor Shc and the transcription factor STAT5 in IL-2Rbeta-deficient mice resulted in production of a normal proportion of natural Treg cells that suppressed severe autoimmunity related with deficiency in IL-2 or IL-2R. These mutant IL-2Rbeta chains supported suboptimal and transient STAT5 activation that upregulate the transcription factor Foxp3 to normal amounts in natural, but not induced, Treg cells. Using cells T cell obtained from normal C57BL/6 mice and mice harboring Treg cells with impaired IL-2R signaling, gene expression profiling revealed many targets in peripheral natural Treg cells that were IL-2-dependent and a substantial overlap between the Treg cell IL-2-dependent gene program and the Treg cell transcriptional signature. Collectively, these findings demonstrate that a critical, and perhaps minor, subset of IL-2-dependent targets in Treg cells is indexed to a low IL-2R signaling threshold and that a substantial proportion of the Treg cell gene program is regulated by IL-2. CD4 T effector cells also showed many IL-2R-dependent gene and these also overlapped in a distintive manner with the IL-2-dependent genes of Treg cells and the Treg gene signature.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 19185518   Authors: Yu A,Zhu L,Altman NH,Malek TR
Exact source GSE14350_1119_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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