Abstract
We examined the role of γδ T cells in the induction of alternatively activated M2 macrophages and the resolution of inflammation after ozone exposure. Wildtype (WT) mice and mice deficient in γδ T cells (TCRδ-/- mice) were exposed to air or to ozone (0.3 ppm for up to 72h) and euthanized immediately or 1, 3, or 5 days after cessation of exposure. In WT mice, M2 macrophages accumulated in the lungs over the course of ozone exposure. Pulmonary mRNA abundance of the M2 genes, Arg1, Retnla, and Clec10a, also increased after ozone. In contrast, no evidence of M2 polarization was observed in TCRδ-/- mice. WT but not TCRδ-/- mice expressed the M2c polarizing cytokine, IL-17A, after ozone exposure and WT mice treated with an IL-17A neutralizing antibody exhibited attenuated ozone-induced M2 gene expression. In WT mice, ozone-induced increases in bronchoalveolar lavage neutrophils and macrophages resolved quickly after cessation of ozone exposure returning to air exposed levels within 3 days. However, lack of M2 macrophages in TCRδ-/- mice was associated with delayed clearance of inflammatory cells after cessation of ozone and increased accumulation of apoptotic macrophages in the lungs. Delayed restoration of normal lung architecture was also observed in TCRδ-/- mice. In summary, our data indicate that γδ T cells are required for the resolution of ozone-induced inflammation, likely because γδ T cells, through their secretion of IL-17A, contribute to changes in macrophage polarization that promote clearance of apoptotic cells.
Highlights
Exposure to the air pollutant, ozone (O3), has a significant impact on human health
To determine whether the decrease in M2 macrophages in TCRδ-/- mice was associated with increased activity of M1 macrophages, we measured bronchoalveolar lavage (BAL) TNFα (Fig 1I): TNFα is predominately expressed by M1 macrophages [36]
We have previously reported that γδ T cells contribute to the pulmonary recruitment of neutrophils and macrophages that occurs after subacute O3 exposure in mice [28]
Summary
O3 exposure causes respiratory symptoms, reductions in lung function, and may even increase the risk of mortality in those with preexisting lung disease [1,2,3,4,5,6]. O3 causes oxidative stress and subsequent damage to lung and airway epithelial cells, leading to the production of numerous cytokines and chemokines, and recruitment of neutrophils and macrophages to the lungs [1,7]. 2, 2015 γδ T Cells and Resolution of Ozone-Induced Inflammation subacute O3 exposure (0.3 ppm for 72 h) [8], though some effects of O3 persist even 72 h after a more prolonged exposure [9]. Termination of O3-induced inflammation and repair of damaged lung cells is key to protecting the lung from the cytotoxic effects of inflammatory cells and mediators
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