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A critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation

Nature Immunology volume 2, pages 45–50 (2001)Cite this article

Abstract

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 κB (NF-κB) 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 γ (IFN-γ) production under TH1-differentiating conditions. Inhibition of NF-κB 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.

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Figure 1: p50−/− mice can recruit adoptively transferred TH2 cells to generate airway inflammation.
Figure 2: NF-κB–deficiency impairs GATA-3 expression.
Figure 3: GATA-3 expression in developing TH2 cells requires NF-κB activation.
Figure 4: NF-κB is not required for GATA-3 expression or TH2 cytokine production in committed TH2 cells.
Figure 5: NF-κB–deficiency does not affect T-bet expression and IFN-γ production.

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Acknowledgements

We thank L. Glimcher for the antibody to T-bet. Supported by grants from the NIH (to A. R.).

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  1. Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, 333 Cedar Street, LCI 105, New Haven, CT 06520, USA

    Jyoti Das, Chang-Hung Chen, Liyan Yang, Lauren Cohn, Prabir Ray & Anuradha Ray

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Correspondence to Anuradha Ray.

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Das, J., Chen, CH., Yang, L. et al. A critical role for NF-κB in Gata3 expression and TH2 differentiation in allergic airway inflammation. Nat Immunol 2, 45–50 (2001). https://doi.org/10.1038/83158

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