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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. This Article Full Text (PDF) All Versions of this Article: 2004-08-3228v1 106/3/946    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Renkl, A. C Articles by Weiss, J. M Search for Related Content PubMed PubMed Citation Articles by Renkl, A. C Articles by Weiss, J. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 25, 2004 Accepted March 23, 2005 Osteopontin functionally activates dendritic cells and induces their differentiation towards a Th-1 polarizing phenotype Andreas C Renkl*, Julia Wussler, Thomas Ahrens, Kathe Thoma, Shigeyuki Kon, Toshimitsu Uede, Stefan F Martin, Jan C Simon, and Johannes M Weiss Department of Dermatology and Allergology, University of Ulm, Ulm, Germany Department of Dermatology, University of Freiburg, Freiburg, Germany Biozentrum Basel, University of Basel, Basel, Switzerland Institute of Genetic Medicine, Hokkaido University, Hokkaido, Japan Department of Dermatology, Venerology and Allergology, University of Leipzig, Leipzig, Germany * Corresponding author; email: andreas.Renkl{at}medizin.uni-ulm.de. Osteopontin (OPN) has been shown to have 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 (DC) are central for the induction of T cell mediated immunity, when initially flexible DC 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 DC from the epidermis and functionally activates myeloid type DC, augmenting their expression of HLA-DR, costimulatory and adhesion molecules, inducing their Th1 promoting TNF- and IL-12 secretion and enhancing their allostimulatory capacity. In MLR OPN stimulates IL-12 secretion by DC, inducing elevated IFN- production by T cells. Naive Th cells stimulated by OPN activated DC show a Th1 polarized cytokine production. Our findings identify OPN as an important tissue-derived factor that DC encounter, when traveling from peripheral sites of activation to secondary lymphatic organs which induces DC maturation towards a Th1 promoting phenotype. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. G. Holtan, D. J. Creedon, P. Haluska, and S. N. Markovic Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic Agents Mayo Clin. Proc., November 1, 2009; 84(11): 985 - 1000. [Abstract] [Full Text] [PDF] Q. Yu, R. Vazquez, E. V. Khojeini, C. Patel, R. Venkataramani, and D. F. Larson IL-18 induction of osteopontin mediates cardiac fibrosis and diastolic dysfunction in mice Am J Physiol Heart Circ Physiol, July 1, 2009; 297(1): H76 - H85. [Abstract] [Full Text] [PDF] A. Prasse, M. Stahl, G. Schulz, G. Kayser, L. Wang, K. Ask, J. Yalcintepe, A. Kirschbaum, E. Bargagli, G. Zissel, et al. Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases Am. J. Pathol., May 1, 2009; 174(5): 1683 - 1691. [Abstract] [Full Text] [PDF] G. Murugaiyan, A. Mittal, and H. L. Weiner Increased Osteopontin Expression in Dendritic Cells Amplifies IL-17 Production by CD4+ T Cells in Experimental Autoimmune Encephalomyelitis and in Multiple Sclerosis J. Immunol., December 1, 2008; 181(11): 7480 - 7488. [Abstract] [Full Text] [PDF] F. W. Kiefer, M. Zeyda, J. Todoric, J. Huber, R. Geyeregger, T. Weichhart, O. Aszmann, B. Ludvik, G. R. Silberhumer, G. Prager, et al. Osteopontin Expression in Human and Murine Obesity: Extensive Local Up-Regulation in Adipose Tissue but Minimal Systemic Alterations Endocrinology, March 1, 2008; 149(3): 1350 - 1357. [Abstract] [Full Text] [PDF] K. X. Wang, Y. Shi, and D. T. Denhardt Osteopontin regulates hindlimb-unloading-induced lymphoid organ atrophy and weight loss by modulating corticosteroid production PNAS, September 11, 2007; 104(37): 14777 - 14782. [Abstract] [Full Text] [PDF] M. Hashimoto, D. Sun, S. R. Rittling, D. T. Denhardt, and W. Young Osteopontin-Deficient Mice Exhibit Less Inflammation, Greater Tissue Damage, and Impaired Locomotor Recovery from Spinal Cord Injury Compared with Wild-Type Controls J. Neurosci., March 28, 2007; 27(13): 3603 - 3611. [Abstract] [Full Text] [PDF] M. L. Shinohara, M. Jansson, E. S. Hwang, M. B. F. Werneck, L. H. Glimcher, and H. Cantor T-bet-dependent expression of osteopontin contributes to T cell polarization PNAS, November 22, 2005; 102(47): 17101 - 17106. [Abstract] [Full Text] [PDF] B. Abel, S. Freigang, M. F. Bachmann, U. Boschert, and M. Kopf Osteopontin Is Not Required for the Development of Th1 Responses and Viral Immunity J. Immunol., November 1, 2005; 175(9): 6006 - 6013. 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