Abstract
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-13Ralpha1-IL-4Ralpha 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-4Ralpha 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-4Ralpha 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Asthma / genetics
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Asthma / immunology
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Bronchial Hyperreactivity / etiology
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Bronchial Hyperreactivity / genetics
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Bronchial Hyperreactivity / immunology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Chemokine CCL11
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Chemokines, CC*
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Cytokines / metabolism
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Cytokines / physiology
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Immunophenotyping
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Interleukin-13 / administration & dosage
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Interleukin-13 / deficiency
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Interleukin-13 / genetics
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Interleukin-13 / physiology*
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Intubation, Intratracheal
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Mice
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Mice, Inbred BALB C
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Mice, Knockout
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Receptors, Interleukin-4 / deficiency
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Receptors, Interleukin-4 / genetics
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Receptors, Interleukin-4 / physiology*
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / immunology
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Respiratory Hypersensitivity / etiology
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Respiratory Hypersensitivity / genetics
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Respiratory Hypersensitivity / immunology*
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STAT6 Transcription Factor
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets
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Th1 Cells / metabolism
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Th1 Cells / transplantation
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Th2 Cells / metabolism
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Th2 Cells / transplantation
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Trans-Activators / deficiency
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Trans-Activators / genetics
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Trans-Activators / physiology
Substances
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Ccl11 protein, mouse
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Chemokine CCL11
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Chemokines, CC
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Cytokines
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Interleukin-13
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Receptors, Interleukin-4
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Recombinant Proteins
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STAT6 Transcription Factor
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Stat6 protein, mouse
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Trans-Activators