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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

Group V Secretory Phospholipase A2 Reveals Its Role in House Dust Mite-Induced Allergic Pulmonary Inflammation by Regulation of Dendritic Cell Function

TL;DR: The expression of group V sPLA2 in APCs regulates Ag processing and maturation of DCs and contributes to pulmonary inflammation and immune response against D. farinae, and an additional yet to be identified resident cell type is essential for the development of pulmonary inflammation.
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Epithelial reticulon 4B (Nogo-B) is an endogenous regulator of Th2-driven lung inflammation.

TL;DR: The reticulon protein Nogo-B is highly expressed in the lungs, and its loss augments lung inflammation in part as a result of decreased expression of the antiinflammatory protein PLUNC.
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Astragalus Membranaceus prevents airway hyperreactivity in mice related to Th2 response inhibition.

TL;DR: Results indicate Astragalus Membranaceus has a potential role in treating allergic asthma, and significantly decreased inflammatory infiltration and mucus secretion in the lung tissues of allergic mice.
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Calcium Channel Blocker Prevents T Helper Type 2 Cell–mediated Airway Inflammation

TL;DR: Nicardipine improves experimental asthma by impairing Th2-dependent inflammation and could provide a rationale for developing drugs selectively targeting DHP receptors of Th2 lymphocytes, potentially beneficial in the treatment of asthma.
Journal ArticleDOI

Fgr Deficiency Results in Defective Eosinophil Recruitment to the Lung During Allergic Airway Inflammation

TL;DR: Results identify Fgr as a novel pharmacological target to control allergic inflammation and suggest that deficiency of Fgr results in a marked reduction of lung eosinophilia and the establishment of a positive feedback loop based on autocrine secretion of eOSinophil-active cytokines.
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.
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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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