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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

T-helper type 2 cell-directed therapy for asthma

TL;DR: The evidence implicating Th2 cells in asthma is reviewed and the cellular and molecular mechanisms that control Th2 cell differentiation in the respiratory tract are discussed, based on the steps in Th cell development, to discuss how traditional therapies can modulate Th2cell function.
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Role of Macrophage Migration Inhibitory Factor in the Th2 Immune Response to Epicutaneous Sensitization

TL;DR: Examining the role of macrophage migration inhibitory factor in the generation of the Th2 response using MIF-deficient mice in a model of epicutaneous sensitization to ovalbumin suggests that MIF is crucial both for the sensitization and the elicitation phases of a Th2-type immune response in allergic disease.
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Relationship between various cytokines implicated in asthma

TL;DR: The main focus of this review is to accentuate the relationship between various cytokines implicated in human asthma, however, some key findings from animal models will be highlighted to support the discoveries from clinical studies.
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The adaptor protein insulin receptor substrate 2 inhibits alternative macrophage activation and allergic lung inflammation

TL;DR: A critical inhibitory loop downstream of IRS2 is identified, demonstrating an unanticipated and previously unrecognized role for IRS2 in suppressing allergic lung inflammation and remodeling.
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Delineating the role of histamine-1- and -4-receptors in a mouse model of Th2-dependent antigen-specific skin inflammation.

TL;DR: A model establishing an adoptive transfer model for antigen-specific Th cells shows a role for H1- and H4-receptors in Th2 cell infiltration and cytokine secretion in allergic skin diseases and suggests further studies to evaluate these findings for therapeutic approaches.
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.
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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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