Blockade of Wnt/?-Catenin Pathway Aggravated Silica-Induced Lung Inflammation through Tregs Regulation on Th Immune Responses.

ABSTRACT: CD4(+) T cells play an important role in regulating silica-induced inflammation and fibrosis. Recent studies showed that Wnt/?-catenin pathway could modulate the function and the differentiation of CD4(+) T cells. Therefore, Wnt/?-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/?-catenin pathway, we used lentivirus expressing ?-catenin shRNA to block the Wnt/?-catenin pathway by intratracheal instillation to the mice model of silicosis. Treatment of lentivirus could significantly aggravate the silica-induced lung inflammation and attenuated the fibrosis at the late stage. By analyzing CD4(+) T cells, we found that blockade of Wnt/?-catenin pathway suppressed regulatory T cells (Tregs). Reciprocally, enhanced Th17 response was responsible for the further accumulation of neutrophils and production of proinflammatory cytokines. In addition, blockade of Wnt/?-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/?-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/?-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.

SUBMITTER: Dai W 

PROVIDER: S-EPMC4812397 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature