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IL-17A–Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis

2010; American Association of Immunologists; Volume: 184; Issue: 11 Linguagem: Inglês

10.4049/jimmunol.0900459

1550-6606

Sandra Lo Re, Laure Dumoutier, Isabelle Couillin, Charlotte Van Vyve, Yousof Yakoub, Francine Uwambayinema, Benoît Marien, Sybille van den Brûle, Jacques Van Snick, Catherine Uyttenhove, Bernard Ryffel, Jean‐Christophe Renauld, Dominique Lison, François Huaux,

Psoriasis: Treatment and Pathogenesis

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, γδ T cell-deficient or CD4+ T cell-depleted mice. In addition, γδ 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-β 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.