Conditional Knockout of the RNA-Binding Protein HuR in CD4 + T Cells Reveals a Gene Dosage Effect on Cytokine Production

摘要: The posttranscriptional mechanisms by which RNA binding proteins (RBPs) regulate T-cell differentiation and cytokine production in vivo remain unclear. RBP HuR binds to labile mRNAs, usually leading increases mRNA stability and/or translation. Previous work demonstrated that the mRNAs encoding Th2 transcription factor trans-acting T-cell-specific (GATA-3) cytokines interleukin (IL)-4 IL-13, thereby regulating their expression. By using a novel conditional knockout (KO) mouse is deleted activated T cells, we show Th2-polarized cells from heterozygous (OX40-Cre HuRfl/+) KO mice had decreased steady-state levels of Gata3, Il4 Il13 with little changes at protein level. Surprisingly, homozygous HuRfl/fl) showed increased Il2, via different mechanisms. Specifically, was transcriptionally upregulated whereas Il2 stabilities increased. Additionally, when standard ovalbumin model allergic airway inflammation, mounted robust inflammatory response similar wild-type levels. These results reveal complex differential regulation gene dosage plays an important role. findings may have significant implications allergies asthma, as well autoimmune diseases infection.