title: Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype.
abstract: Osteopontin (OPN) has been shown to have T helper 1 (Th1) cytokine functions in cell-mediated immunity. Deficiency of OPN is linked to a reduced Th1 immune response in autoimmunity, infectious disease, and delayed-type allergy. Dendritic cells (DCs) are central for the induction of T-cell-mediated immunity, when initially flexible DCs are instructed by priming signals and tissue-derived factors to adopt Th1, Th2, or regulatory T-cell-inducing phenotypes. Although OPN influences the cytokine secretion of T cells and macrophages, its effects on DC polarization remain an important missing link in the understanding of OPN functions in Th1 immunity. Here we demonstrate that OPN promotes the emigration of human DCs from the epidermis and functionally activates myeloid-type DCs, augmenting their expression of HLA-DR, costimulatory, and adhesion molecules. OPN induces their Th1-promoting tumor necrosis factor alpha (TNF-alpha) and interleukin-12 (IL-12) secretion, and enhances their allostimulatory capacity. In mixed lymphocyte reactions (MLRs), OPN stimulates IL-12 secretion by DCs, inducing elevated interferon-gamma (IFN-gamma) production by T cells. Naive Th cells stimulated by OPN-activated DCs show a Th1-polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DCs encounter when traveling from peripheral sites of activation to secondary lymphatic organs, which induces DC maturation toward a Th1-promoting phenotype.
authors.affiliation: University of Ulm, Department of Dermatology and Allergology, Maienweg 12, 89081 Ulm, Germany. andreas.renkl@medizin.uni-ulm.de
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Renkl
authors.forename: Julia
authors.initials: J
authors.lastname: Wussler
authors.forename: Thomas
authors.initials: T
authors.lastname: Ahrens
authors.forename: Käthe
authors.initials: K
authors.lastname: Thoma
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kon
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Martin
authors.forename: Jan C
authors.initials: JC
authors.lastname: Simon
authors.forename: Johannes M
authors.initials: JM
authors.lastname: Weiss
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007801:Langerhans Cells / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D053495:Osteopontin; D010641:Phenotype; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000494:pharmacology*; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; D011994:Recombinant Proteins; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin