Lo Re S, Dumoutier L, Couillin I, van Vyve C, Yakoub Y, Uwambayinema F, Marien B, van der Brûle S, van Snick J, Uyttenhove C, Ryffel B, Renauld JC, Lison D, Huaux F.IL-17A-Producing γδ T and Th17 Lymphocytes Mediate Lung Inflammation but Not Fibrosis in Experimental Silicosis. The Journal of Immunology. 2010 Apr 26;184(11):6367–77.

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, γd T cell-deficient or CD4+ T cell-depleted mice. In addition, γd 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. [/toggle_content]

Clodronate Concentration Total Lipid Concentration Lipid Composition Lipid Mole % Liposome Type Control Liposomes
5 mg/ml 23.5 mg/ml EPC/Chol 86/14 MLV PBS
Animal Description Clodronate Dose Dosing Method/Site Target Phagocytes Systemic Dosing? Systemic Results
C57BL/6 mice2 100 µl pharyngeal aspiration / lungs alveolar macrophages (AM) no not evaluated

2Base or background strain. Variants, mutants or otherwise genetically altered strains were also used in this study.

Notes

  1. No details on pharyngeal dosing technique published.
  2. Citations related to macrophage depletion compare intratracheal and aerosol administration methods, not pharyngeal administration.

Results

  1. >80% of the AM were depleted (BAL cell counts via light microscopy) 3 days post-treatment (data not shown).
  2. Complete inhibition of IL-7A production is only other depletion-related data published.