Human Gene Set: GSE23505_UNTREATED_VS_4DAY_IL6_IL1_TGFB_TREATED_CD4_TCELL_DN


Standard name GSE23505_UNTREATED_VS_4DAY_IL6_IL1_TGFB_TREATED_CD4_TCELL_DN
Systematic name M7868
Brief description Genes down-regulated in CD4 [GeneID=920] T cells: untreated versus IL6 and TGFB1 [GeneID=3569;7040].
Full description or abstract CD4+ T cells that selectively produce interleukin (IL)-17, are critical for host defense and autoimmunity1-4. Crucial for T helper17 (Th17) cells in vivo5,6, IL-23 has been thought to be incapable of driving initial differentiation. Rather, IL-6 and transforming growth factor (TGF)-?1 have been argued to be the factors responsible for initiating specification7-10. Herein, we show that Th17 differentiation occurs in the absence of TGF-? signaling. Neither IL-6 nor IL-23 alone efficiently generated Th17 cells; however, these cytokines in combination with IL-1? effectively induced IL-17 production in naïve precursors, independently of TGF-?. Epigenetic modification of the Il17a/Il17f and Rorc promoters proceeded without TGF-?1, allowing the generation of cells that co-expressed Ror?t and T-bet. T-bet+Ror?t+ Th17 cells are generated in vivo during experimental allergic encephalomyelitis (EAE), and adoptively transferred Th17 cells generated with IL-23 in the absence of TGF-?1 were more pathogenic in this experimental disease. These data suggest a new model for Th17 differentiation. Consistent with genetic data linking the IL23R with autoimmunity, our findings re-emphasize the role of IL-23 and therefore have important implications for the development of new therapies.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 20962846   Authors: Ghoreschi K,Laurence A,Yang XP,Tato CM,McGeachy MJ,Konkel JE,Ramos HL,Wei L,Davidson TS,Bouladoux N,Grainger JR,Chen Q,Kanno Y,Watford WT,Sun HW,Eberl G,Shevach EM,Belkaid Y,Cua DJ,Chen W,O'Shea JJ
Exact source GSE23505_2886_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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