A 3' enhancer in the IL-4 gene regulates cytokine production by Th2 cells and mast cells.

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, V(A), 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 V(A). 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.

journal_name

Immunity

journal_title

Immunity

authors

Solymar DC,Agarwal S,Bassing CH,Alt FW,Rao A

doi

10.1016/s1074-7613(02)00334-5

keywords:

subject

Has Abstract

pub_date

2002-07-01 00:00:00

pages

41-50

issue

1

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(02)00334-5

journal_volume

17

pub_type

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