Posttranscriptional gene regulation of CD4+ T cell cytokine expression by the RNA binding protein HuR

Abstract

[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.