| First Author | Seki N | Year | 2004 |
| Journal | J Immunol | Volume | 172 |
| Issue | 10 | Pages | 6158-66 |
| PubMed ID | 15128803 | Mgi Jnum | J:89872 |
| Mgi Id | MGI:3041768 | Doi | 10.4049/jimmunol.172.10.6158 |
| Citation | Seki N, et al. (2004) IL-4-induced GATA-3 expression is a time-restricted instruction switch for Th2 cell differentiation. J Immunol 172(10):6158-66 |
| abstractText | An initial activation signal via the TCR in a restricted cytokine environment is critical for the onset of Th cell development. Cytokines regulate the expression of key transcriptional factors, T-bet and GATA-3, which instruct the direction of Th1 and Th2 differentiation, through changes in chromatin conformation. In this study, we investigated the kinetics of IL-4-mediated signaling in a transgenic mouse, expressing human IL-4R on a mouse IL-4alphaR-deficient background. These experiments, allowing induction with human IL-4 at defined times, demonstrated that an IL-4 signal was required at the early stage of TCR-mediated T cell activation for lineage commitment to Th2, along with structural changes in chromatin, which take place in the conserved noncoding sequence-1 and -2 within the IL-4 locus. At later times, however, IL-4 failed to promote efficient Th2 differentiation and decondensation of chromatin, even though GATA-3 was clearly induced in the nuclei by IL-4 stimulation. Moreover, IL-4-mediated Th2 instruction was independent from cell division mediated by initial TCR stimulation. The role of IL-4 signaling may have a time restriction during Th2 differentiation. In late stages of initial T cell activation, the chromatin structure of the IL-4 locus retains condensation state. These results demonstrate that IL-4-induced GATA-3 expression is time-restriction switch for Th2 differentiation. |
