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] [custom_table]
| 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.
[/custom_table]Notes
- No details on pharyngeal dosing technique published.
- Citations related to macrophage depletion compare intratracheal and aerosol administration methods, not pharyngeal administration.
Results
- >80% of the AM were depleted (BAL cell counts via light microscopy) 3 days post-treatment (data not shown).
- Complete inhibition of IL-7A production is only other depletion-related data published.