Journal
JOURNAL OF IMMUNOLOGY
Volume 177, Issue 5, Pages 3421-3426Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.177.5.3421
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Funding
- NCI NIH HHS [1R01CA91839] Funding Source: Medline
- NIAID NIH HHS [1R01AI43433] Funding Source: Medline
- NIDDK NIH HHS [R01DK059380, R01 DK059380] Funding Source: Medline
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The mast cell (MC) inflammatory response is now linked not only to atopy, but also to arthritis, multiple sclerosis, heart disease, and resistance to bacterial infection. In the current study, we demonstrate that the signal transducer and activator of transcription 5 (Stat5) is rapidly activated by IgE cross-linkage, and that its expression is critical to the MC response. Stat5-deficient (Stat5KO) MC demonstrated a significant decrease in IgE-mediated degranulation, leukotriene B, production, cytokine secretion, and survival signals. The defect in cytokine production may be caused by decreased cytokine mRNA stability. Stat5KO MC-induced cytokine mRNAs normally following IgE cross-linkage, but these mRNAs were not sustained over time and were degraded at twice the rate observed in WT cells. Interestingly, the RNA destabilizing protein tristetraprolin was induced following IgE cross-linkage in Stat5KO but not wild-type cells. Moreover, reducing tristetraprolin expression via short hairpin RNA transfection significantly increased IL-13 production in Stat5KO MC. Our work demonstrates that Stat5 is a critical factor in IgE-induced MC activation, acting in part via posttranscriptional control of cytokine mRNA stability. These data have a direct impact on MC-associated inflammatory and autoimmune diseases.
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