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Blood, 1 August 2005, Vol. 106, No. 3, pp. 946-955.
Prepublished online as a Blood First Edition Paper on April 26, 2005; DOI 10.1182/blood-2004-08-3228.
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IMMUNOBIOLOGY
Osteopontin functionally activates dendritic cells and induces their differentiation toward a Th1-polarizing phenotype
Andreas C. Renkl,
Julia Wussler,
Thomas Ahrens,
Käthe Thoma,
Shigeyuki Kon,
Toshimitsu Uede,
Stefan F. Martin,
Jan C. Simon, and
Johannes M. Weiss
From the Department of Dermatology and Allergology, University of Ulm, Germany; the Department of Dermatology, University of Freiburg, Germany; the Biozentrum Basel, University of Basel, Switzerland; the Institute for Genetic Medicine, Hokkaido University, Japan; and the Department of Dermatology, Venerology and Allergology, University of Leipzig, Germany.
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  (TNF-) 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- (IFN-) 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.
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