title: Effects of DKK-3, a Wnt signaling inhibitor, on dendritic cell phenotype and T cell polarization.
abstract: Wnt signaling plays crucial roles in regulation of a wide range of processes in different cell types including immune cells and, in particular, dendritic cells and T cells. Growing indications point out that Wnt pathway components modulate the both innate and adaptive immune responses through regulating DC functions. We investigated the effects of recombinant DKK-3 protein on the phenotype and biological functions of bone marrow-derived DCs (BM-DCs) as well as T cell polarization. The phenotype and the cytokine production of BM-derived DCs in the presence DKK-3 were analyzed using flow cytometry and ELISA, respectively. Also, capability of DCs to activate T cells was evaluated by CFSE-labeled splenocytes. Regulatory T cell induction, T cell polarization, and cytokine secretion were assessed by flow cytometry and ELISA in splenocytes cultured in the presence of DKK-3. Our results showed that the expression of CD86 and CD40 increased in the DKK-3-treated DC, while the expression of PDL-1 and PDL-2 diminished. Furthermore, the presence of DKK-3 decreased IL-10 and IL-4 production and increased IFN-gamma production by treated DCs.DKK-3. Moreover, DKK-3 shifted naive CD4 T cells towards TH1 cells through up-regulation of T-bet and down-regulation of GATA-3. Our results, therefore, suggest that DKK-3 protein has the ability to promote the generation of Th1-immunostimulatory DCs from its precursors.
authors.affiliation: a Department of Medical Immunology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran .
authors.forename: Hemn
authors.initials: H
authors.lastname: Mohammadpour
authors.affiliation: a Department of Medical Immunology, Faculty of Medical Sciences , Tarbiat Modares University , Tehran , Iran .
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Pourfathollah
authors.affiliation: b Blood Transfusion Research Center, High Institute for Research and Education in Transfusion Medicine , Tehran , Iran , and.
authors.forename: Mahin
authors.initials: M
authors.lastname: Nikougoftar Zarif
authors.affiliation: c Department of Immunology, Faculty of Medicine , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
authors.forename: Mohammad Taher
authors.initials: MT
authors.lastname: Tahoori
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D018417:Th1 Cells / Q000187:drug effects / Q000502:physiology; D060449:Wnt Signaling Pathway / Q000187:drug effects / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins
keywords: DKK-3; Dendritic cells; T cells; Wnt signaling; regulatory T cells