Immunity
Volume 17, Issue 1, July 2002, Pages 41-50
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Article
A 3′ Enhancer in the IL-4 Gene Regulates Cytokine Production by Th2 Cells and Mast Cells

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Abstract

Differentiation of naive T cells into mature Th2 cells is associated with the appearance of a complex pattern of DNase I hypersensitive (DH) sites within the IL-4/IL-13 cytokine gene cluster. We show here that targeted deletion of an inducible DH site, VA, and the adjacent conserved DH site V (CNS-2) selectively compromises IL-4 gene transcription by differentiated Th2 cells and mast cells. In mast cells, the deletion abrogates IL-4 mRNA induction, an effect mimicked by deletion of the transcription factor NFAT1 (NFATc2), which binds DH site VA. In T cells, the deletion impairs a process of response maturation, defined by progressive increases in IL-4 levels as Th2 differentiation proceeds. These results identify an essential enhancer which regulates IL-4 gene expression in two important cell lineages in vivo.

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These authors contributed equally to this work.