Human Gene Set: GSE39382_IL3_VS_IL3_IL33_TREATED_MAST_CELL_DN


Standard name GSE39382_IL3_VS_IL3_IL33_TREATED_MAST_CELL_DN
Systematic name M9539
Brief description Genes down-regulated in bone marrow-derived mast cells treated with IL3 [GeneID=3562]: control versus IL33 [GeneID=90865].
Full description or abstract Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its acute effects on mouse mast cells (MCs), IL-33 is thought to play a role in the pathogenesis of allergic disease through MC activation. However, the manifestations of chronic IL-33 exposure on human MC function, which best reflect the conditions associated with chronic allergic disease, are unknown. We now find that long-term exposure of human and mouse MCs to IL-33 results in a substantial reduction of MC activation in response to antigen. This reduction required >72 h exposure to IL-33 for onset and 1-2 wk for reversion following IL-33 removal. This hypo-responsive phenotype was determined to be a consequence of MyD88-dependent attenuation of signaling processes necessary for MC activation including antigen-mediated calcium mobilization and cytoskeletal reorganization; potentially as a consequence of down-regulation of the expression of PLCg1 and Hck. These findings suggest that IL-33 may play a protective, rather than a causative role in MC activation under chronic conditions and, furthermore, reveal regulated plasticity in the MC activation phenotype. The ability to down-regulate MC activation in this manner may provide alternative approaches for treatment of MC-driven disease.
Collection C7: Immunologic Signature
      IMMUNESIGDB: ImmuneSigDB
Source publication Pubmed 23248261   Authors: Jung MY,Smr? D,Desai A,Bandara G,Ito T,Iwaki S,Kang JH,Andrade MV,Hilderbrand SC,Brown JM,Beaven MA,Metcalfe DD,Gilfillan AM
Exact source GSE39382_2750_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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