ArrayExpress Uploader06948interleukin 3interleukin 3interleukin 3interleukin 3interleukin 3interleukin 3interleukin 3 and interleukin 33interleukin 3 and interleukin 33interleukin 3 and interleukin 33interleukin 3 and interleukin 33interleukin 3 and interleukin 33interleukin 3 and interleukin 33arrayexpress_sid6Interleukin-33 (IL-33) is elevated in afflicted tissues of patients with mast cell-dependent chronic allergic diseases. Based on its...23248261E-GEOD-39382/profile/8773/arrayexpressuploader112bonebone marrowcelldiseaseinterleukinmast cellDec.12, 2014Falseil-33-induces-a-hypo-responsive-human-mast-cell-phE-GEOD-39382_A-AFFY-45IL-33 induces a hypo-responsive human mast cell phenotypeNov.12, 2014Interleukin-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. Mouse bone marrow-derived mast cells treated with IL3 or IL3+IL33. 6 replicates each.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-39382mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-39382/samples/