ArrayExpress Uploader06762interleukin-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-33interleukin-3 and stem cell factorinterleukin-3 and stem cell factorinterleukin-3 and stem cell factorinterleukin-3 and stem cell factorinterleukin-3 and stem cell factorinterleukin-3 and stem cell factorarrayexpress_sid6Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that...22529299E-GEOD-35332/profile/8773/arrayexpressuploader118asthmabonebone marrowcellcytokinediseasemast cellproteinstem cellDec.12, 2014FalseE-GEOD-35332_A-AFFY-45stem-cell-factor-programs-the-mast-cell-activationStem cell factor programs the mast cell activation phenotypeNov.12, 2014Mast cells, activated by antigen via the high affinity receptor for IgE (FcεRI), release an array of pro-inflammatory mediators that contribute to allergic disorders such as asthma and anaphylaxis. The KIT ligand, stem cell factor (SCF), is critical for mast cell expansion, differentiation and survival, and, under acute conditions, enhances mast cell activation. However, extended SCF exposure in vivo conversely protects against fatal antigen-mediated anaphylaxis. In investigating this dichotomy, we identified a novel mode of regulation of the mast cell activation phenotype through SCF-mediated programming. We found that mouse bone marrow-derived mast cells chronically exposed to SCF displayed a marked attenuation of FcεRI-mediated degranulation and cytokine production. The hypo-responsive phenotype was not a consequence of altered signals regulating calcium flux or protein kinase C, but of ineffective cytoskeletal reorganization, with evidence implicating a down-regulation of expression of the Src kinase Hck. Collectively, these findings demonstrate a major role for SCF in the homeostatic control of mast cell activation with potential relevance to mast cell-driven disease and the development of novel approaches for the treatment of allergic disorders. Mouse bone marrow-derived mast cells were treated with IL3, IL3+IL33, or IL3+SCF. Six replicates each.http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-35332mousehttp://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-35332/samples/