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IL-17A-producing gammadelta T and Th17 lymphocytes mediate lung inflammation but not fibrosis in experimental silicosis.

Authors: Lo Re, S  Dumoutier, L  Couillin, I  Van Vyve, C  Yakoub, Y  Uwambayinema, F  Marien, B  Van den Brule, S  Van Snick, J  Uyttenhove, C  Ryffel, B  Renauld, JC  Lison, D  Huaux, F 
Citation: Lo Re S, etal., J Immunol. 2010 Jun 1;184(11):6367-77. Epub 2010 Apr 26.
Pubmed: (View Article at PubMed) PMID:20421647
DOI: Full-text: DOI:10.4049/jimmunol.0900459

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.


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CRRD Object Information
CRRD ID: 4888525
Created: 2010-11-23
Species: All species
Last Modified: 2010-11-23
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.