J. Das et al., A critical role for NF-kappa B in Gata3 expression and T(H)2 differentiation in allergic airway inflammation, NAT IMMUNOL, 2(1), 2001, pp. 45-50
The transcription factor GATA-3 is expressed in T helper 2 (T(H)2) but not
T(H)1 cells and plays a critical role in T(H)2 differentiation and allergic
airway inflammation in vivo. Mice that lack the p50 subunit of nuclear fac
tor kappaB (NF-kappaB) are unable to mount airway eosinophilic inflammation
. We show here that this is not due to defects in TH2 cell recruitment but
due to the inability of the p50(-/-) mice to produce interleukin 4 (IL-4),
IL-5 and IL-13: cytokines that play distinct roles in asthma pathogenesis.
CD4(+) T cells from p50(-/-) mice failed to induce Gata3 expression under T
(H)2-differentiating conditions but showed unimpaired T-bet expression and
interferon gamma (IFN-gamma) production under T(H)1-differentiating conditi
ons. Inhibition of NF-kappaB activity prevented GATA-3 expression and T(H)2
cytokine production in developing, but not committed,T(H)2 cells. Our stud
ies provide a molecular basis for the need for both T cell receptor and cyt
okine signaling for GATA-3 expression and, in turn,T(H)2 differentiation.