Stat5 expression is required for IgE-mediated mast cell function.
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 B4 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.
Barnstein
Brian O
BO
Department of Biology, Virginia Commonwealth University, Richmond, VA 23284, USA.
Li
Geqiang
G
Wang
Zhengqi
Z
Kennedy
Sarah
S
Chalfant
Charles
C
Nakajima
Hiroshi
H
Bunting
Kevin D
KD
Ryan
John J
JJ
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007073:Immunoglobulin E / Q000276:immunology*; D015289:Leukotrienes / Q000096:biosynthesis; D008407:Mast Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D020871:RNA Stability / Q000235:genetics; D017455:Receptors, IgE / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051816:Tristetraprolin / Q000378:metabolism
D016207:Cytokines; D015289:Leukotrienes; D017455:Receptors, IgE; D050799:STAT5 Transcription Factor; D051816:Tristetraprolin; D007073:Immunoglobulin E; D048049:Extracellular Signal-Regulated MAP Kinases