A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation.
The transcription factor GATA-3 is expressed in T helper 2 (TH2) but not TH1 cells and plays a critical role in TH2 differentiation and allergic airway inflammation in vivo. Mice that lack the p50 subunit of nuclear factor kappa B (NF-kappa B) 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 TH2-differentiating conditions but showed unimpaired T-bet expression and interferon gamma (IFN-gamma) production under TH1-differentiating conditions. Inhibition of NF-kappa B activity prevented GATA-3 expression and TH2 cytokine production in developing, but not committed, TH2 cells. Our studies provide a molecular basis for the need for both T cell receptor and cytokine signaling for GATA-3 expression and, in turn, TH2 differentiation.
Das
J
J
Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, 333 Cedar Street, LCI 105, New Haven, CT 06520, USA.
Chen
C H
CH
Yang
L
L
Cohn
L
L
Ray
P
P
Ray
A
A
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000235:genetics*; D004195:Disease Models, Animal; D050990:GATA3 Transcription Factor; D015870:Gene Expression; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D050800:STAT6 Transcription Factor; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators