| First Author | Wenner CA | Year | 1997 |
| Journal | J Immunol | Volume | 158 |
| Issue | 2 | Pages | 765-73 |
| PubMed ID | 8992993 | Mgi Jnum | J:40450 |
| Mgi Id | MGI:87794 | Doi | 10.4049/jimmunol.158.2.765 |
| Citation | Wenner CA, et al. (1997) Identification of IL-4 promoter elements conferring Th2-restricted expression during T helper cell subset development. J Immunol 158(2):765-73 |
| abstractText | Selective cytokine gene expression by T cell subsets underlies polarization of cellular and humoral immune responses. Our interest has been to define the molecular basis for restricted cytokine expression by Th1 and Th2 cells. IL-4 is selectively expressed by Th2 cells, providing a model for Th2-specific gene expression. To allow for promoter analysis during the process of Th1/Th2 differentiation within a normal cellular context, we have taken a transgenic approach. We generated a series of murine transgenic lines harboring both the DO11.10 alphabeta-TCR transgene and the luciferase gene driven by regions of the IL-4 promoter. The results identify proximal promoter regions that provide significantly Th2-restricted IL-4 gene expression. The IL-4 -741- to +60-bp region allows, on the average, 40-fold higher inducible reporter activity in Th2 cells than in Th1 cells. When trimerized, the region spanning -88 to -61 bp, containing a composite NF-AT/AP-1 site, also confers significant Th2-specific reporter activity. These results suggest that trans-acting factors binding this NF-AT/AP-1 composite site cooperate to allow substantial Th2-selective reporter expression. Finally, because reporter expression is low relative to endogenous IL-4 mRNA in activated Th2 cells, we suggest that additional control elements outside of the IL-4 promoter may be required to enhance overall IL-4 gene activity. |
