title: Blockade of Wnt/β-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/β-catenin pathway could modulate the function and the differentiation of CD4(+) T cells. Therefore, Wnt/β-catenin pathway may participate in the development and progress of silicosis. To investigate the role of Wnt/β-catenin pathway, we used lentivirus expressing β-catenin shRNA to block the Wnt/β-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/β-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/β-catenin pathway delayed the Th1/Th2 polarization by inhibiting Tregs and Th2 response. These results indicated that Wnt/β-catenin pathway could regulate Tregs to modulate Th immune response, which finally altered the pathological character of silicosis. Our study suggested that Wnt/β-catenin pathway might be a potential target to treat the silica-induced inflammation and fibrosis.
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Wujing
authors.initials: W
authors.lastname: Dai
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Fangwei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Li
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Sitong
authors.initials: S
authors.lastname: Du
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Weng
authors.affiliation: Division of Pneumoconiosis, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang 110122, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000502:physiology; D012822:Silicon Dioxide; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics / Q000502:physiology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D051176:beta Catenin; D012822:Silicon Dioxide