Wnt/β-catenin pathway promotes acute lung injury induced by LPS through driving the Th17 response in mice

T helper cell 17 (Th17), one type of CD4(+) T cell, plays an important role in regulating the acute lung injury (ALI) inflammatory response. Recent studies showed that Wnt/beta-catenin pathway could modulate the differentiation and the function of CD4(+) T cell. However, whether Wnt/beta-catenin could regulate the differentiation and function of Th17 in the development and progress of ALI induced by lipopolysaccharide (LPS) is still unknown. To test this, we used dickkopfl (Dkk-1) to block the Wnt/beta-catenin pathway and LiCI to activate the Wnt/beta-catenin pathway by instillation to the murine model of ALI. Our results revealed that activation of Wnt/beta-catenin pathway significantly aggravated the LPS-induced lung inflammation. Meanwhile, we observed that activation of Wnt/fi-catenin pathway promoted Th17 response by analyzing CD4(+) T cells and the related cytokines secretions. Enhanced Th17 response was responsible for the further neutrophils infiltration and pro-inflammatory cytokines production. In addition, activation of Wnt/beta-catenin pathway resulted in induced expression of retinoic acid related orphan receptor-gamma t (RORyt) via histone acetyltransferase p300. These data suggested that Wnt/beta-catenin pathway might be a potential target to treat the LPS-induced inflammation in ALI. (C) 2017 Elsevier Inc. All rights reserved.