Abstract
BackgroundSilicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored.Methodology/Principal FindingsTo evaluate the role of Th17 and IL-17 in the development of silicosis and their interaction with Tregs, Treg-depleted mice model was generated and exposed to silica to establish experimental model of silica-induced lung fibrosis. Here we showed that silica increased Th17 response in lung fibrosis. Tregs depletion enhanced the neutrophils accumulation and attenuated Th17 response in silica induced lung fibrosis. Both mRNA and protein results showed that Tregs exerted its modulatory function on Th17 cells and IL-17 by regulating TGF-β1 and IL-1β.Conclusion/SignificanceOur study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-β1 and IL-1β in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation.
Highlights
Inhalation of silica particle caused silicosis, which is characterized by lung inflammation and fibrosis [1,2]
Conclusion/Significance: Our study suggested that Tregs could promote Th17 cells differentiation by regulating TGF-b1 and IL-1b in silica induced lung fibrosis of mice, which further the understanding of the progress of silicosis and provide a new insight in the regulatory mechanism of Th17 by Tregs in lung inflammation
The level of IL-4 in Treg-depleted group was lower than that in silica-treated group (Figure S5 D). These results suggested that Th1 cells and/or Th1 cytokines benefited from the severer neutrophilic inflammation in experimental model of silica-induced lung fibrosis in the absence of Tregs; since the differentiation of Th17 cells could be inhibited by the Th1 cytokine [12], enhancement of Th1 cytokines might inhibit Th17 differentiation and IL-17 secretion
Summary
Inhalation of silica particle caused silicosis, which is characterized by lung inflammation and fibrosis [1,2]. We reported a crucial role of Tregs in silicosis that depletion of Tregs could attenuate the progress of silica-induced lung fibrosis [5]. Silicosis is an occupational lung disease caused by inhalation of silica dust and characterized by lung inflammation and fibrosis. Previous study showed that Tregs regulate the process of silicosis by modulating the maintenance of immune homeostasis in the lung. Th17 cells share reciprocal developmental pathway with Tregs and play a pivotal role in the immunopathogenesis of many lung diseases by recruiting and activating neutrophils, but the regulatory function of Tregs on Th17 response in silica induced lung fibrosis remains to be explored
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