Human Gene Set: GSE35543_IN_VIVO_NTREG_VS_CONVERTED_EX_ITREG_DN


Standard name GSE35543_IN_VIVO_NTREG_VS_CONVERTED_EX_ITREG_DN
Systematic name M9434
Brief description Genes down-regulated in comparison between in vivo derived natural T reg (nTreg) and converted ex-iTreg (induced T reg that lost FOXP3 [GeneID=50943] expression).
Full description or abstract Induced Treg (iTreg) cells are essential for tolerance and can be used therapeutically, yet their stability in vivo and mechanisms of suppression are unresolved. Here, we used a treatment model of colitis to examine the role of autologous IL-10 in iTreg cell function. Mice treated with IL-10+/+ iTreg cells in combination with IL-10?/? natural Treg (nTreg) cells survived and gained weight, even though iTreg cells were numerically disadvantaged and comprised just ~20% of all Treg cells in treated mice. Notably, ~85% of the transferred iTreg cells lost Foxp3 expression (ex-iTreg) but retained a portion of the iTreg transcriptome which failed to limit their pathogenic potential. The TCR repertoires of iTreg and ex-iTreg cells exhibited almost no overlap, which indicates that the two populations are clonally unrelated and maintained by different selective pressures. These data demonstrate a potent and critical role for iTreg cell produced IL-10 that can supplant the IL-10 produced by nTreg cells and compensate for the inherent instability of the iTreg population.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 23125413   Authors: Schmitt EG,Haribhai D,Williams JB,Aggarwal P,Jia S,Charbonnier LM,Yan K,Lorier R,Turner A,Ziegelbauer J,Georgiev P,Simpson P,Salzman NH,Hessner MJ,Broeckel U,Chatila TA,Williams CB
Exact source GSE35543_3050_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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