Abstract
The etiology of asthma, a chronic inflammatory disorder of the airways, remains obscure, although T cells appear to be central disease mediators. Lyn tyrosine kinase has been implicated as both a facilitator and inhibitor of signaling pathways that play a role in allergic inflammation, although its role in asthma is unclear because Lyn is not expressed in T cells. We show in the present study that Lyn-/- mice develop a severe, persistent inflammatory asthma-like syndrome with lung eosinophilia, mast cell hyperdegranulation, intensified bronchospasm, hyper IgE, and Th2-polarizing dendritic cells. Dendritic cells from Lyn-/- mice have a more immature phenotype, exhibit defective inhibitory signaling pathways, produce less IL-12, and can transfer disease when adoptively transferred into wild-type recipients. Our results show that Lyn regulates the intensity and duration of multiple asthmatic traits and indicate that Lyn is an important negative regulator of Th2 immune responses.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Allergens / administration & dosage
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Allergens / immunology
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Animals
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Asthma / enzymology*
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Asthma / genetics
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Asthma / immunology*
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Asthma / pathology
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B-Lymphocyte Subsets / enzymology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / pathology
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Bronchial Spasm / enzymology
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Bronchial Spasm / genetics
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Bronchial Spasm / immunology
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Bronchial Spasm / physiopathology
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Cells, Cultured
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Dendritic Cells / enzymology
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Dendritic Cells / immunology
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Down-Regulation / genetics
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Down-Regulation / immunology*
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Immunity, Mucosal / genetics
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Immunoglobulin E / physiology
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Inflammation Mediators / administration & dosage
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Inflammation Mediators / immunology
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Lung / enzymology
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Lung / immunology
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Lung / pathology
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Mast Cells / enzymology
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Mast Cells / immunology
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Mast Cells / pathology
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Th2 Cells / enzymology
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Th2 Cells / immunology*
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Th2 Cells / pathology
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src-Family Kinases / deficiency*
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src-Family Kinases / genetics*
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src-Family Kinases / physiology
Substances
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Allergens
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Inflammation Mediators
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Immunoglobulin E
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Ovalbumin
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lyn protein-tyrosine kinase
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src-Family Kinases