Posttranscriptional gene regulation of CD4+ T cell cytokine expression by the RNA binding protein HuR
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[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Posttranscriptional gene regulation by RNA-binding proteins such as HuR fine tunes gene expression in T cells leading to powerful effects on immune responses. HuR can stabilize target mRNAs and/or promote translation by interacting with their 3’UTR AUrich elements. We discovered that the interaction of HuR with the Il2ra (CD25) mRNA transcript is required for its optimal translation. Conditional HuR knockout (KO) in CD4+ T cells resulted in loss of IL-2 homeostasis and defects in Th2 cytokine production. In an allergic airway inflammatory model, OVA-challenged HuR KO mice had decreased lung cellular infiltration, eosinophilia and IL-13. These results demonstrate that HuR plays a pivotal role in maintaining normal IL-2 homeostasis, augmenting Th2 differentiation and promoting allergic airway inflammation.