IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis.
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.
Lo Re
Sandra
S
Louvain Centre for Toxicology and Applied Pharmacology, de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Dumoutier
Laure
L
Couillin
Isabelle
I
Van Vyve
Charlotte
C
Yakoub
Yousof
Y
Uwambayinema
Francine
F
Marien
Benoît
B
van den Brûle
Sybille
S
Van Snick
Jacques
J
Uyttenhove
Catherine
C
Ryffel
Bernard
B
Renauld
Jean-Christophe
JC
Lison
Dominique
D
Huaux
François
F
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*
D020381:Interleukin-17; D012333:RNA, Messenger; D016692:Receptors, Antigen, T-Cell, gamma-delta