title: The translational repressor T-cell intracellular antigen-1 (TIA-1) is a key modulator of Th2 and Th17 responses driving pulmonary inflammation induced by exposure to house dust mite.
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.
authors.affiliation: Department of Medicine, Harvard Medical School, and Division of Rheumatology, Immunology and Allergy, Brigham and Women’s Hospital, Boston, MA 02115, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Simarro
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giannattasio
authors.forename: Wei
authors.initials: W
authors.lastname: Xing
authors.forename: Emma-Maria
authors.initials: EM
authors.lastname: Lundequist
authors.forename: Samantha
authors.initials: S
authors.lastname: Stewart
authors.forename: Richard L
authors.initials: RL
authors.lastname: Stevens
authors.forename: Antonio
authors.initials: A
authors.lastname: Orduña
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Boyce
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Anderson
mesh_terms: D000281:Administration, Intranasal; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology; D002465:Cell Movement; D002678:Chimera / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D040001:Dermatophagoides farinae / Q000737:chemistry / Q000276:immunology*; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D020397:Goblet Cells; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000139:chemically induced / Q000150:complications / Q000276:immunology* / Q000473:pathology; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D000074019:T-Cell Intracellular Antigen-1; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D007074:Immunoglobulin G; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C499367:Tia1 protein, mouse; D007073:Immunoglobulin E