Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation

Citation
By. Li et al., Regulation of IL-4 expression by the transcription factor JunB during T helper cell differentiation, EMBO J, 18(2), 1999, pp. 420-432
Citations number
50
Categorie Soggetti
Molecular Biology & Genetics
Journal title
EMBO JOURNAL
ISSN journal
02614189 → ACNP
Volume
18
Issue
2
Year of publication
1999
Pages
420 - 432
Database
ISI
SICI code
0261-4189(19990115)18:2<420:ROIEBT>2.0.ZU;2-B
Abstract
The molecular basis for restricted cytokine expression by T helper 1 (Th1) and T helper 2 (Th2) cells is unclear. Previous studies found that P1, an e lement of the interleukin 4 (IL-4) promoter that binds AP-1, is important f or Th2-restricted IL-4 expression. Here we show that JunB, but not the othe r Jun family members, was selectively induced in Th2 cells and not in Th1 c ells during differentiation. JunB has previously been considered to be a ne gative regulator of transcription. However, we show that JunB binds directl y to the P1 site and synergizes with c-Maf to activate an IL-4 luciferase r eporter gene. JunB-control of IL-4 expression is mediated by the phosphoryl ation of JunB at Thr102 and -104 by JNK MAP kinase, The synergy between c-M af and JunB can be attributed to cooperative DNA binding, which is facilita ted by JunB phosphorylation, In transgenic mice, elevated JunB levels cause d increased expression of several Th2 cytokines in developing Th1 cells. Ju nB also upregulated IL-4 expression in response to immunization. Thus, the early increase of JunB protein in Th2 cells can provide the specificity for c-Maf in IL-4 expression during T cell development and directs thereby Th2 differentiation.