A stat-6- binding element in the IL-4 promoter

H. Huang*, J. Hu-Li, S. Z. Ben-Sasson, R. Seder, W. E. Paul

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

In vitro, the major determinant of whether a naive T cell becomes an IL-4-producer is IL-4 itself. Recently, it has been demonstrated that IL4 causes the activation of STAT-6. For this reason, it was of particular interest to note that three potential STAT-binding (GAS) elements existed in both the mouse and human IL-4 promoters. We designated these sites 4GL1,4GL2 and 4GL3. 4GL3 bound to extracts from IL-4-treated T and B cells. This complex was supershifted by anti-STAT-6 antibody. Furthermore, 4GL3 efficiently competed with binding to STAT-6 of GAS elements from the CD23 and the IE promoters. By contrast, neither 4GL2 nor 4GL1 bound to cell extracts in an IL-4-inducible manner. To test the potential role of 4GL3 in the production of IL-4 by T cells that had recently developed into IL-4 producers, we differentiated naive CD4+ T cells into TH1 and TH2 cells; these cells were transfected utilizing particle bombardment with a luciferase reporter construct under the control of IL-4 promoter elements containing or lacking 4GL3. Luciferase activtiy of both constructs was induced by immobilized anti-CD3 in TH2 but not TH1 cells. This suggests that IL-4 production in response to TCR stimulation by recently differentiated TH2 cells does not require 4GL3. Blocking the activity of IL-4 with either anti-IL-4 or anti-IL-4 receptor antibody did not diminish IL-4 production by TH2 cells in response to TCR stimulation, nor did IL-4 enhance IL-4 production in response to limiting amounts of antigen. We conclude that IL-4 does not play an important role in IL-4 production by recently differentiated TH2 cells in response to TCRmediated activation. The possible role of 4GL3 in the commitment of naive T cells to IL-4 production is under active study.

Original languageEnglish
Pages (from-to)A1311
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

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