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Open AccessJournal ArticleDOI

Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production

TLDR
It is suggested that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.
Abstract
Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4–deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-α, IL-4 −/− Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

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Journal ArticleDOI

Interleukin-13: Central Mediator of Allergic Asthma

TL;DR: In this paper, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal Article

Interleukin-13: Central mediator of allergic asthma

TL;DR: In this article, the type 2 cytokine IL-13, which shares a receptor component and signaling pathways with IL-4, was found to be necessary and sufficient for the expression of allergic asthma.
Journal ArticleDOI

Requirement for IL-13 Independently of IL-4 in Experimental Asthma

TL;DR: This article showed that IL-4 receptor α chain-dependent pathway may underlie the genetic associations of asthma with both the human 5q31 locus and the IL4 receptor and showed that selective neutralization of IL-13, a cytokine related to interleukin-4 that also binds to the α chain of the IL 4 receptor, ameliorated asthma phenotype.
Journal ArticleDOI

Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production

TL;DR: The targeted pulmonary expression of IL-13 causes a mononuclear and eosinophilic inflammatory response, mucus cell metaplasia, airway fibrosis, eotaxin production, airways obstruction, and nonspecific AHR in transgene-positive animals.
Journal ArticleDOI

The immunology of asthma

TL;DR: Results from in-depth molecular studies of mouse models in light of the results from the first clinical trials targeting key cytokines in humans are discussed and the extraordinary heterogeneity of asthma is described.
References
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Journal ArticleDOI

Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors.

TL;DR: Blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half, and mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eOSinophilia.
Journal ArticleDOI

CD4 T-lymphocyte activation in acute severe asthma. Relationship to disease severity and atopic status.

TL;DR: The serum concentrations of interferon-gamma and soluble IL-2R were significantly elevated in patients with acute severe asthma as compared with all the control groups and decreased as the patients improved clinically during the first 3-day period of hospital treatment.
Journal ArticleDOI

Interleukin-4 is required for the induction of lung Th2 mucosal immunity.

TL;DR: IL-4 is central both to the induction of a local Th2 response and to the development of eosinophilic inflammation of the lung, with a sequential involvement of IL-4 and IL-5.
Journal ArticleDOI

CD4+ T-lymphocytes and interleukin-5 mediate antigen-induced eosinophil infiltration into the mouse trachea.

TL;DR: Results provide direct evidence that CD4+ but not CD8+ T-cells mediate antigen-induced eosinophil recruitment in the airways and that IL-5 mediates this eos inophil recruited in the trachea.
Journal ArticleDOI

Suppression of in vivo polyclonal IgE responses by monoclonal antibody to the lymphokine B-cell stimulatory factor 1.

TL;DR: Results indicate an important physiologic role for BSF-1 in the generation of IgE antibody responses and suggest means for limiting the production of antibodies responsible for allergic reactions without inhibiting protective antibody responses.
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