| The IL-3/IL-5/GM-CSF common receptor plays a pivotal role in the regulation of Th2 immunity and allergic airway inflammation. | |
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MedLine Citation:
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PMID: 18178860 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The eosinophil is a central effector cell in allergic asthma. Differentiation and function of eosinophils are regulated by the CD4 Th2 cytokines IL-3, IL-5, and GM-CSF, which all signal through a common beta receptor subunit (betac). Recent therapeutic approaches targeting IL-5 alone have not ablated tissue accumulation of eosinophils and have had limited effects on disease progression, suggesting important roles for IL-3 and GM-CSF. By using a mouse model of allergic airways inflammation, we show that allergen-induced expansion and accumulation of eosinophils in the lung are abolished in betac-deficient (betac-/-) mice. Moreover, betac deficiency resulted in inhibition of hallmark features of asthma, including airways hypersensitivity, mucus hypersecretion, and production of Ag-specific IgE. Surprisingly, we also identified a critical role for this receptor in regulating type 2 immunity. Th2 cells in the lung of allergen-challenged betac-/- mice were limited in their ability to proliferate, produce cytokines, and migrate to effector sites, which was attributed to reduced numbers of myeloid dendritic cells in the lung compartment. Thus, the betac plays a critical role in allergen-induced eosinophil expansion and infiltration and is pivotal in regulating molecules that promote both early and late phases of allergic inflammation, representing a novel target for therapy. |
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Authors:
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Kelly L Asquith; Hayley S Ramshaw; Philip M Hansbro; Kenneth W Beagley; Angel F Lopez; Paul S Foster |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 180 ISSN: 0022-1767 ISO Abbreviation: J. Immunol. Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2008-01-07 Completed Date: 2008-03-10 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 1199-206 Citation Subset: AIM; IM |
Affiliation:
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Centre for Asthma and Respiratory Diseases, School of Biomedical Sciences, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, Callaghan, Australia. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Allergens
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immunology Animals Asthma / genetics, immunology* Cell Movement Cytokine Receptor Common beta Subunit / genetics, physiology* Cytokines / metabolism Dendritic Cells / immunology Eosinophils / immunology Granulocyte-Macrophage Colony-Stimulating Factor / metabolism Interleukin-3 / metabolism Interleukin-5 / metabolism Lymphocyte Activation Macrophages, Alveolar / immunology Mice Mice, Mutant Strains Respiratory Hypersensitivity / genetics, immunology* Signal Transduction Th2 Cells / immunology* |
| Grant Support | |
ID/Acronym/Agency:
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R01-AI50744-02/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Allergens; 0/Cytokine Receptor Common beta Subunit; 0/Cytokines; 0/Interleukin-3; 0/Interleukin-5; 83869-56-1/Granulocyte-Macrophage Colony-Stimulating Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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