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Role of TCR-Induced Extracellular Signal-Regulated Kinase Activation in the Regulation of Early IL-4 Expression in Naive CD4+ T Cells
| Content Provider | Scilit |
|---|---|
| Author | Jorritsma, Patricia J. Brogdon, Jennifer L. Bottomly, Kim |
| Copyright Year | 2003 |
| Description | Although extracellular signal-regulated kinase (Erk) activation influences IL-4 production in various experimental systems, its role during Th differentiation is unclear. In this study, we show that Erk plays a critical role in IL-4 expression during TCR-induced Th differentiation of naive $CD4^{+}$ T cells. Stimulation of $CD4^{+}$ T cells with a high affinity peptide resulted in sustained Erk activation and Th1 differentiation. However, reduction of Erk activity led to a dramatic increase in IL-4 production and Th2 generation. Analysis of RNA and nuclear proteins of $CD4^{+}$ T cells 48 h after stimulation revealed that this was due to early IL-4 expression. Interestingly, transient Erk activation resulted in altered AP-1 DNA binding activity and the induction of an AP-1 complex that was devoid of Fos protein and consisted of Jun-Jun dimers. These data show that in the presence of a strong TCR signal, IL-4 expression can be induced in naive $CD4^{+}$ T cells by altering the strength of Erk activation. In addition, these data suggest that TCR-induced Erk activation is involved in the regulation of IL-4 expression by altering the composition of the AP-1 complex and its subsequent DNA binding activity. |
| Ending Page | 2434 |
| Page Count | 8 |
| Starting Page | 2427 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.170.5.2427 |
| Journal | The Journal of Immunology |
| Issue Number | 5 |
| Volume Number | 170 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2003-03-01 |
| Access Restriction | Open |
| Subject Keyword | Naive Cd4 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
