title: Wnt5a signaling increases IL-12 secretion by human dendritic cells and enhances IFN-γ production by CD4+ T cells.
abstract: Wnt5a is a secreted pleiotropic glycoprotein produced in an inflammatory state by a wide spectrum of ubiquitous cell populations. Recently, we demonstrated that Wnt5a skews the differentiation of human monocyte derived dendritic cells (moDCs) to a tolerogenic functional state. In this study we focus our interest on the role of this Wnt ligand after DC differentiation, during their maturation and function. We show that the expression of Wnt receptors is tightly regulated during the life cycle of DCs suggesting a differential responsiveness to Wnt signaling conditioned by their differentiation stage and the maturational stimuli. Furthermore, we confirm that Wnt5a is the main non-canonical Wnt protein expressed by DCs and its production increases upon specific stimuli. Exogenous Wnt5a improved the endocytic capacity of immature DCs but it is not a stimulatory signal on its own, slightly affecting the maturation and function of DCs. However, knocking down Wnt5a gene expression in maturing DCs demonstrates that DC-derived Wnt5a is necessary for normal IL-12 secretion and plays a positive role during the development of Th1 responses. Wnt5a acts both in autocrine and paracrine ways. Thus, human naive CD4(+) T cells express Wnt receptors and, the addition of Wnt5a during CD3/CD28 stimulation enhances IL-2 and IFN-γ production. Taken together these results suggest a time-dependent role for Wnt5a during inflammatory responses conditioned by the differentiation stage of cellular targets.
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Jaris
authors.initials: J
authors.lastname: Valencia
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Víctor G
authors.initials: VG
authors.lastname: Martínez
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Hidalgo
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Hernández-López
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Noelia M
authors.initials: NM
authors.lastname: Canseco
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Vicente
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Varas
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain. Electronic address: rmsacedo@ucm.es.
authors.forename: Rosa
authors.initials: R
authors.lastname: Sacedón
mesh_terms: D019898:Autocrine Communication; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008024:Ligands; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D060490:Receptors, Wnt / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D000071818:Wnt-5a Protein; D060528:Wnt4 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D008024:Ligands; D011518:Proto-Oncogene Proteins; D060490:Receptors, Wnt; D051193:Toll-Like Receptors; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C540523:Wnt11 protein, human; D060528:Wnt4 Protein; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: DCs; IFN-γ; IL-10; IL-12; T-cell; Wnt