title: IL-13 induces airways hyperreactivity independently of the IL-4R alpha chain in the allergic lung.
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.
authors.affiliation: Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT 0200, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Mattes
authors.forename: M
authors.initials: M
authors.lastname: Yang
authors.forename: A
authors.initials: A
authors.lastname: Siqueira
authors.forename: K
authors.initials: K
authors.lastname: Clark
authors.forename: J
authors.initials: J
authors.lastname: MacKenzie
authors.forename: A N
authors.initials: AN
authors.lastname: McKenzie
authors.forename: D C
authors.initials: DC
authors.lastname: Webb
authors.forename: K I
authors.initials: KI
authors.lastname: Matthaei
authors.forename: P S
authors.initials: PS
authors.lastname: Foster
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology; D016535:Bronchial Hyperreactivity / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines / Q000378:metabolism / Q000502:physiology; D016130:Immunophenotyping; D018793:Interleukin-13 / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007442:Intubation, Intratracheal; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019948:Receptors, Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D050800:STAT6 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets; D018417:Th1 Cells / Q000378:metabolism / Q000637:transplantation; D018418:Th2 Cells / Q000378:metabolism / Q000637:transplantation; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000502:physiology
chemical_list: C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D016207:Cytokines; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators