First Author | Cook KD | Year | 2010 |
Journal | J Immunol | Volume | 185 |
Issue | 6 | Pages | 3209-16 |
PubMed ID | 20696860 | Mgi Jnum | J:175335 |
Mgi Id | MGI:5285154 | Doi | 10.4049/jimmunol.0902544 |
Citation | Cook KD, et al. (2010) TCR-dependent translational control of GATA-3 enhances Th2 differentiation. J Immunol 185(6):3209-16 |
abstractText | The differentiation of CD4(+) T cells into the Th2 subset is controlled by the transcription factor GATA-3. GATA-3 is both necessary and sufficient for Th2 differentiation and works through the induction of chromatin remodeling at the Th2 effector cytokine loci. We show in this study that IL-4 stimulation induces GATA-3 mRNA upregulation, but the level of GATA-3 protein induced is insufficient for Th2 differentiation. The levels of GATA-3 protein and Th2 differentiation are enhanced by concomitant TCR signaling through the PI3K/mammalian target of rapamycin pathway. The PI3K-mediated increase in GATA-3 protein occurs without increasing the GATA-3 mRNA level. Rather, TCR signaling through PI3K specifically enhances the translation rate of GATA-3 without affecting the protein stability. Importantly, this role of TCR signaling is independent of the effects of TCR signaling in T cell survival and expansion. Thus, TCR signaling through PI3K may play a critical role in Th2 differentiation by the specific enhancement of GATA-3 translation. |