Human Gene Set: GSE19198_CTRL_VS_IL21_TREATED_TCELL_24H_DN


Standard name GSE19198_CTRL_VS_IL21_TREATED_TCELL_24H_DN
Systematic name M7231
Brief description Genes down-regulated in T cells: control (0h) versus IL21 [GeneID=59067] for 24h.
Full description or abstract Interleukin-21 (IL-21) is a pleiotropic cytokine that induces expression of transcription factor BLIMP1 (encoded by Prdm1), which regulates plasma cell differentiation and T cell homeostasis. We identified an IL-21 response element downstream of Prdm1 that binds the transcription factors STAT3 and IRF4, which are required for optimal Prdm1 expression. Genome-wide ChIP-Seq mapping of STAT3- and IRF4-binding sites showed that most regions with IL-21-induced STAT3 binding also bound IRF4 in vivo, and furthermore, revealed that the noncanonical TTCnnnTAA GAS motif critical in Prdm1 was broadly used for STAT3 binding. Comparing genome-wide expression array data to binding sites revealed that most IL-21-regulated genes were associated with combined STAT3-IRF4 sites rather than pure STAT3 sites. Correspondingly, ChIP-Seq analysis of Irf4_/_ T cells showed greatly diminished STAT3 binding after IL-21 treatment, and Irf4_/_ mice showed impaired IL- 21-induced Tfh cell differentiation in vivo. These results reveal broad cooperative gene regulation by STAT3 and IRF4.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20064451   Authors: Kwon H,Thierry-Mieg D,Thierry-Mieg J,Kim HP,Oh J,Tunyaplin C,Carotta S,Donovan CE,Goldman ML,Tailor P,Ozato K,Levy DE,Nutt SL,Calame K,Leonard WJ
Exact source GSE19198_2366_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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