title: IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis.
abstract: IL-17-producing T lymphocytes play a crucial role in inflammation, but their possible implication in fibrosis remains to be explored. In this study, we examined the involvement of these cells in a mouse model of lung inflammation and fibrosis induced by silica particles. Upregulation of IL-17A was associated with the development of experimental silicosis, but this response was markedly reduced in athymic, gammadelta T cell-deficient or CD4(+) T cell-depleted mice. In addition, gammadelta T lymphocytes and CD4(+) T cells, but not macrophages, neutrophils, NK cells or CD8 T cells, purified from the lungs of silicotic mice markedly expressed IL-17A. Depletion of alveolar macrophages or neutralization of IL-23 reduced upregulation of IL-17A in the lung of silicotic mice. IL-17R-deficient animals (IL-17R(-/-)) or IL-17A Ab neutralization, but not IL-22(-/-) mice, developed reduced neutrophil influx and injury during the early lung response to silica. However, chronic inflammation, fibrosis, and TGF-beta expression induced by silica were not attenuated in the absence of IL-17R or -22 or after IL-17A Ab blockade. In conclusion, a rapid lung recruitment of IL-17A-producing T cells, mediated by macrophage-derived IL-23, is associated with experimental silicosis in mice. Although the acute alveolitis induced by silica is IL-17A dependent, this cytokine appears dispensable for the development of the late inflammatory and fibrotic lung responses to silica.
authors.affiliation: Louvain Centre for Toxicology and Applied Pharmacology, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lo Re
authors.forename: Laure
authors.initials: L
authors.lastname: Dumoutier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Couillin
authors.forename: Charlotte
authors.initials: C
authors.lastname: Van Vyve
authors.forename: Yousof
authors.initials: Y
authors.lastname: Yakoub
authors.forename: Francine
authors.initials: F
authors.lastname: Uwambayinema
authors.forename: Benoît
authors.initials: B
authors.lastname: Marien
authors.forename: Sybille
authors.initials: S
authors.lastname: van den Brûle
authors.forename: Jacques
authors.initials: J
authors.lastname: Van Snick
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Bernard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Renauld
authors.forename: Dominique
authors.initials: D
authors.lastname: Lison
authors.forename: François
authors.initials: F
authors.lastname: Huaux
mesh_terms: D000818:Animals; D002469:Cell Separation; D004195:Disease Models, Animal; D005434:Flow Cytometry; D020381:Interleukin-17 / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D016133:Polymerase Chain Reaction; D011658:Pulmonary Fibrosis / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta; D012829:Silicosis / Q000276:immunology* / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D020381:Interleukin-17; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta