Gene Set: GAVIN_PDE3B_TARGETS

Standard name GAVIN_PDE3B_TARGETS
Systematic name M1737
Brief description Genes changed in peripheral regulatory T lymphocytes that depend on PDE3B [GeneID=5140].
Full description or abstract Regulatory CD4+ T cells (Tr cells), the development of which is critically dependent on X-linked transcription factor Foxp3 (forkhead box P3), prevent self-destructive immune responses. Despite its important role, molecular and functional features conferred by Foxp3 to Tr precursor cells remain unknown. It has been suggested that Foxp3 expression is required for both survival of Tr precursors as well as their inability to produce interleukin (IL)-2 and independently proliferate after T-cell-receptor engagement, raising the possibility that such 'anergy' and Tr suppressive capacity are intimately linked. Here we show, by dissociating Foxp3-dependent features from those induced by the signals preceding and promoting its expression in mice, that the latter signals include several functional and transcriptional hallmarks of Tr cells. Although its function is required for Tr cell suppressor activity, Foxp3 to a large extent amplifies and fixes pre-established molecular features of Tr cells, including anergy and dependence on paracrine IL-2. Furthermore, Foxp3 solidifies Tr cell lineage stability through modification of cell surface and signalling molecules, resulting in adaptation to the signals required to induce and maintain Tr cells. This adaptation includes Foxp3-dependent repression of cyclic nucleotide phosphodiesterase 3B, affecting genes responsible for Tr cell homeostasis.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 17220874   Authors: Gavin MA,Rasmussen JP,Fontenot JD,Vasta V,Manganiello VC,Beavo JA,Rudensky AY
Exact source Supplementary Fig 8E
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Organism Mus musculus
Contributed by Jessica Robertson (Broad Institute)
Source platform MOUSE_GENE_SYMBOL
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Compendia expression profiles Human tissue compendium (Novartis)
NCI-60 cell lines (National Cancer Institute)
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Version history 3.1: First introduced

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