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Chain in the Allergic Lung1
*
Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, Australia; and
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom
The potent spasmogenic properties of IL-13 have identified this
molecule as a potential regulator of airways hyperreactivity (AHR) in
asthma. Although IL-13 is thought to primarily signal through the
IL-13R
1-IL-4R complex, the cellular and molecular components
employed by this cytokine to induce AHR in the allergic lung have not
been identified. By transferring OVA-specific CD4+ T cells
that were wild type (IL-13+/+ T cells) or deficient in
IL-13 (IL-13-/- T cells) to nonsensitized mice that were
then challenged with OVA aerosol, we show that T cell-derived IL-13
plays a key role in regulating AHR, mucus hypersecretion, eotaxin
production, and eosinophilia in the allergic lung. Moreover,
IL-13+/+ T cells induce these features (except mucus
production) of allergic disease independently of the IL-4R chain. By
contrast, IL-13+/+ T cells did not induce disease in
STAT6-deficient mice. This shows that IL-13 employs a novel component
of the IL-13 receptor signaling system that involves STAT6,
independently of the IL-4R chain, to modulate pathogenesis. We show
that this novel pathway for IL-13 signaling is dependent on T cell
activation in the lung and is critically linked to downstream effector
pathways regulated by eotaxin and STAT6.
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