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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

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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 Article

Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins.

TL;DR: A panel of antigen-specific mouse helper T cell clones was characterized according to patterns of lymphokine activity production, and two types of T cell were distinguished.
Journal ArticleDOI

Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma

TL;DR: Atopic asthma is associated with activation in the bronchi of the interleukin-3, 4, and 5 and GM-CSF gene cluster, a pattern compatible with predominant activation of the TH2-like T-cell population.
Journal ArticleDOI

Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens.

TL;DR: This paper used hybridoma monoclonal antibodies obtained after immunization of mice with rat cells to study rat cell-surface antigens present on subpopulations of rat lymphocytes.
Journal ArticleDOI

Induction by antigen of intrathymic apoptosis of CD4+CD8+TCRlo thymocytes in vivo

TL;DR: Results provide direct evidence for the in vivo role of apoptosis in the development of antigen-induced tolerance in mice transgenic for a T cell receptor that reacts to this peptide.
Journal ArticleDOI

Generation and analysis of interleukin-4 deficient mice.

TL;DR: Some but not all of the in vitro properties of IL-4 are critical for the physiology of the immune system in vivo, but the serum levels of IgG1 and IgE are strongly reduced.
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