title: Type 2 immune response associated with silicosis is not instrumental in the development of the disease.
abstract: It has been proposed that the development of lung fibrosis is associated with a T helper type 2 response, mainly characterized by IL-4 and IL-13 production. We investigated the potential role of type 2 immune polarization in the silicotic process and examined the pulmonary response to silica particles in mice genetically deficient for IL-4. We found that IL-4(-/-) mice were not protected against the development of silicosis, suggesting that IL-4 is not essential for the development of this fibrotic disease. By evaluating the intensity of silica-induced lung fibrosis in mice deficient for IL-4 receptor alpha (IL-4Ralpha), we showed that the establishment of pulmonary fibrosis was independent of both IL-4 and IL-13. Strong impairment of the type 2 immune response (IgG(1)) in the lungs of IL-4(-/-) and IL-4Ralpha(-/-) mice did not affect the development of the disease. Measurement of IL-13alpha2 receptor expression and IgG(2a), IL-12p70, and IFN-gamma levels in silica-treated IL-4(-/-) and IL-4Ralpha(-/-) animals showed that the development of silicosis was not related to an IL-13 signaling pathway or a switch to a type 1 response in deficient animals. Our data clearly indicate that the type 2 immune response associated with silicosis in mice is not required for the development of this inflammatory and fibrotic disease.
authors.affiliation: Unit of Industrial Toxicology and Occupational Medicine, Université Catholique de Louvain, 53.02 Ave. E. Mounier, 1200 Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Misson
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Monique
authors.initials: M
authors.lastname: Delos
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: Francois
authors.initials: F
authors.lastname: Huaux
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics; D012829:Silicosis / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D053662:Interleukin-4 Receptor alpha Subunit
chemical_list: D007074:Immunoglobulin G; D018793:Interleukin-13; D015847:Interleukin-4; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit