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.