Abstract
T-cell intracellular antigen-1 (TIA-1) is a translational repressor that dampens the production of proinflammatory cytokines and enzymes. In this study we investigated the role of TIA-1 in a mouse model of pulmonary inflammation induced by exposure to the allergenic extract (Df) of the house dust mite Dermatophagoides farinae. When intranasally challenged with a low dose of Df, mice lacking TIA-1 protein (Tia-1(-/-)) showed more severe airway and tissue eosinophilia, infiltration of lung bronchovascular bundles, and goblet cell metaplasia than wild-type littermates. Tia-1(-/-) mice also had higher levels of Df-specific IgE and IgG(1) in serum and ex vivo restimulated Tia-1(-/-) lymph node cells and splenocytes transcribed and released more Th2/Th17 cytokines. To evaluate the site of action of TIA-1, we studied the response to Df in bone marrow chimeras. These experiments revealed that TIA-1 acts on both hematopoietic and non-hematopoietic cells to dampen pulmonary inflammation. Our results identify TIA-1 as a negative regulator of allergen-mediated pulmonary inflammation in vivo. Thus, TIA-1 might be an important player in the pathogenesis of bronchial asthma.
Copyright © 2012 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Administration, Intranasal
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Allergens / administration & dosage
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Allergens / immunology
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Animals
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Antigens, Dermatophagoides / administration & dosage
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Antigens, Dermatophagoides / immunology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / pathology
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Cell Movement
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Chimera / immunology
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Cytokines / biosynthesis
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Cytokines / immunology
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Dermatophagoides farinae / chemistry
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Dermatophagoides farinae / immunology*
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Disease Models, Animal
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Eosinophilia / chemically induced
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Eosinophilia / complications
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Eosinophilia / immunology*
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Eosinophilia / pathology
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Goblet Cells
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Immunoglobulin E / blood
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Immunoglobulin E / immunology
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Immunoglobulin G / blood
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Immunoglobulin G / immunology
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Lung / immunology*
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Lung / metabolism
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Lung / pathology
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Male
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Mice
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Mice, Knockout
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Pneumonia / chemically induced
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Pneumonia / complications
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Pneumonia / immunology*
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Pneumonia / pathology
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / immunology*
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T-Cell Intracellular Antigen-1
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Th17 Cells / immunology*
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Th17 Cells / metabolism
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Th2 Cells / immunology*
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Th2 Cells / metabolism
Substances
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Allergens
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Antigens, Dermatophagoides
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Cytokines
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Immunoglobulin G
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RNA-Binding Proteins
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T-Cell Intracellular Antigen-1
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Tia1 protein, mouse
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Immunoglobulin E