Human Gene Set: GSE36888_STAT5_AB_KNOCKIN_VS_WT_TCELL_IL2_TREATED_17H_DN


Standard name GSE36888_STAT5_AB_KNOCKIN_VS_WT_TCELL_IL2_TREATED_17H_DN
Systematic name M8755
Brief description Genes down-regulated in T cells stimulated by IL2 [GeneID=3558] for 17h: STAT5 double knock-in versus wildtype.
Full description or abstract Cytokine-activated STAT proteins dimerize and bind to high-affinity motifs, and N-terminal domain-mediated oligomerization of dimers allows tetramer formation and binding to low-affinity tandem motifs, but the functions of dimers versus tetramers are unknown. We generated Stat5a and Stat5b double knock-in (DKI) N-domain mutant mice that form dimers but not tetramers, identified cytokine-regulated genes whose expression required STAT5 tetramers, and defined consensus motifs for dimers versus tetramers. Whereas Stat5- deficient mice exhibited perinatal lethality, DKI mice were viable, indicating that STAT5 dimers were sufficient for survival. Nevertheless, STAT5 DKI mice had fewer CD4+CD25+ T cells, NK cells, and CD8+ T cells, with impaired cytokine-induced proliferation and homeostatic proliferation of CD8+ T cells. DKI CD8+ T cell proliferation following viral infection was diminished and DKI Treg cells did not efficiently control colitis. Thus, tetramerization of STAT5 is dispensable for survival but is critical for cytokine responses and normal immune function.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 22520852   Authors: Lin JX,Li P,Liu D,Jin HT,He J,Ata Ur Rasheed M,Rochman Y,Wang L,Cui K,Liu C,Kelsall BL,Ahmed R,Leonard WJ
Exact source GSE36888_2363_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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