A critical role for NF-kappa B in Gata3 expression and T(H)2 differentiation in allergic airway inflammation

Citation
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
Citations number
39
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
NATURE IMMUNOLOGY
ISSN journal
1529-2908 → ACNP
Volume
2
Issue
1
Year of publication
2001
Pages
45 - 50
Database
ISI
SICI code
1529-2908(200101)2:1<45:ACRFNB>2.0.ZU;2-7
Abstract
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.