title: Interactions between canonical Wnt signaling pathway and MAPK pathway regulate differentiation, maturation and function of dendritic cells.
abstract: Antigen-presenting dendritic cells interpret environmental signals to orchestrate local and systemic immune responses. In this study, the roles of Wnt proteins and their signaling pathway members in the maturation and function of monocyte-derived DCs were investigated. The present study showed higher expression of β-catenin, as well as pGSK-3β in DCs than those in monocytes. Wnt3a, Wnt5a and inhibition of GSK-3β promoted differentiation of DCs, but inhibited maturation of DCs. GSK-3β induced DCs maturation with unconventional phenotypes. Together with β-catenin silence, these treatment lead to reduced secretion of cytokines and chemokines except for IL-10 in comparison with LPS treatment, and significantly promoted proliferation of T cells. Wnt3a and inhibition of GSK-3β increased expression of MAPK signalings (p-ERK, p-p38, p-JNK). However, inhibition of MAPK signalings in turn differently regulated Wnt signaling proteins expression. These data suggest that Wnt pathway regulates DCs differentiation, maturation and function with interaction of MAPK signaling pathways.
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China.
authors.forename: Wang-Dong
authors.initials: WD
authors.lastname: Xu
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China; Department of General Medicine Center, Sichuan Provincial People's Hospital, Chengdu 610072, Sichuan Province, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China.
authors.forename: Tong-Ling
authors.initials: TL
authors.lastname: Yuan
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Rheumatology and Immunology, West China Hospital, Sichuan University, 37 Guoxue Xiang, Chengdu, Sichuan 610041, China. Electronic address: zhao.y1977@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Institute for Clinical Immunology and Rheumatology, Department of Internal Medicine III, University of Erlangen-Nuremberg, Erlangen 91052, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Herrmann
mesh_terms: D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D009000:Monocytes / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D000071818:Wnt-5a Protein / Q000378:metabolism*; D060509:Wnt3A Protein / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C555510:WNT3A protein, human; C085389:WNT5A protein, human; D000071818:Wnt-5a Protein; D060509:Wnt3A Protein; D051176:beta Catenin; D016753:Interleukin-10; D000071679:Glycogen Synthase Kinase 3 beta; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Dendritic cell; MAPK; NF-κB; Wnt signaling pathway