LFA-1-dependent HuR nuclear export and cytokine mRNA stabilization in T cell activation

Jin Gene Wang, Mark Collinge, Vinod Ramgolam, Oran Ayalon, Xinhao Cynthia Fan, Ruggero Pardi, Jeffrey R. Bender

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphokine gene expression is a precisely regulated process in T cell-mediated immune responses. In this study we demonstrate that engagement of the β2 integrin LFA-1 in human peripheral T cells markedly extends the half-life of TNF-α, GM-CSF, and IL-3 mRNA, as well as a chimeric β-globin mRNA reporter construct containing a strongly destabilizing class II AU-rich element from the GM-CSF mRNA β-untranslated region. This integrin-enhanced mRNA stability leads to augmented protein production, as determined by TNF-α ELISPOT assays. Furthermore, T cell stimulation by LFA-1 promotes rapid nuclear-to-cytoplasmic translocation of the mRNA-stabilizing protein HuR, which in turn is capable of binding an AU-rich element sequence in vitro. Abrogation of HuR function by use of inhibitory peptides, or marked reduction of HuR levels by RNA interference, prevents LFA-1 engagement-mediated stabilization of T cell TNF-α or IFN-γ transcripts, respectively. Thus, HuR-mediated mRNA stabilization, stimulated by integrin engagement and controlled at the level of HuR nuclear export, is critically involved in T cell activation.

Original languageEnglish
Pages (from-to)2105-2113
Number of pages9
JournalJournal of Immunology
Volume176
Issue number4
Publication statusPublished - Feb 15 2006

ASJC Scopus subject areas

  • Immunology

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