Abstract
Epstein-Barr virus-induced gene (EBI)-3 codes for a soluble type 1 cytokine receptor homologous to the p40 subunit of IL-12 that is expressed by antigen-presenting cells following activation. Here, we analyzed the functional role of EBI-3 in a murine model of asthma associated with airway hyper-responsiveness (AHR) in ovalbumin-sensitized mice. Upon allergen challenge, EBI-3-/- mice showed less severe AHR, decreased numbers and degranulation of eosinophils and a significantly reduced number of VCAM-1+ cells in the lungs as compared to wild-type littermates. We thus analyzed lung CD11c+ cells before and after allergen challenge in these mice and found that before allergen challenge, lung CD11c+ cells isolated from EBI-3-/- mice express markers of a more plasmacytoid phenotype without releasing IFN-alpha as compared to those from wild-type littermates. Moreover, allergen challenge induced the development of myeloid CD11c+ cells in the lungs of EBI-3-/- mice, which released increased amounts of IL-10 and IL-12 while not expressing IFN-alpha. Finally, inhibition of EBI-3 expression in lung DC could prevent AHR in adoptive transfer studies by suppressing mediator release of effector cells into the airways. These results indicate a novel role for EBI-3 in controlling local immune responses in the lungs in experimental asthma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Asthma / chemically induced
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Asthma / immunology*
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Asthma / metabolism
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Bronchial Hyperreactivity / genetics
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Bronchial Hyperreactivity / immunology*
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Bronchial Hyperreactivity / physiopathology
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Bronchoalveolar Lavage Fluid / chemistry
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Bronchoalveolar Lavage Fluid / cytology
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CD11c Antigen / analysis*
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Proliferation
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Cell Transplantation / methods
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / transplantation
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Eosinophils / metabolism
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Eosinophils / pathology
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Interferon-alpha / metabolism
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Interferon-gamma / metabolism
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Interleukin-10 / metabolism
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Interleukin-12 / metabolism
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Interleukin-4 / metabolism
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Interleukin-5 / metabolism
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Lung / cytology
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Lung / immunology*
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Lung / metabolism
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Minor Histocompatibility Antigens
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Receptors, Cytokine / genetics*
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STAT4 Transcription Factor / metabolism
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T-Box Domain Proteins / metabolism
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Tumor Necrosis Factor-alpha / metabolism
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Vascular Cell Adhesion Molecule-1 / metabolism
Substances
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CD11c Antigen
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Ebi3 protein, mouse
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Interferon-alpha
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Interleukin-5
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Minor Histocompatibility Antigens
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Receptors, Cytokine
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STAT4 Transcription Factor
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Stat4 protein, mouse
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Tumor Necrosis Factor-alpha
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Vascular Cell Adhesion Molecule-1
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Interleukin-10
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Interleukin-12
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Interleukin-4
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Interferon-gamma