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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2547-2553. Prepublished online as a Blood First Edition Paper on December 11, 2003; DOI 10.1182/blood-2003-09-3058. This Article Full Text (PDF) All Versions of this Article: 2003-09-3058v1 103/7/2547    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 Chen, W. Articles by Liu, Y.-J. Search for Related Content PubMed PubMed Citation Articles by Chen, W. Articles by Liu, Y.-J. Related Collections Related Article in Blood Online Social Bookmarking                   What's this? Submitted September 5, 2003 Accepted November 21, 2003 Thrombopoietin cooperates with FLT3-ligand in the generation of plasmacytoid dendritic cell precursors from human hematopoietic progenitors Wei Chen*, Svetlana Antonenko, Joel M Sederstrom, Xueqing Liang, Anissa S Chan, Holger Kanzler, Bianca Blom, Bruce R Blazar, and Yong-Jun Liu Division of Hematology, Oncology and Bone Marrow Transplantation, University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN, USA Department of Immunobiology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA, USA * Corresponding author; email: chenw{at}umn.edu. Type 1 interferon-producing cells (IPCs), also known as plasmacytoid DC precursors, represent the key effectors in anti-viral innate immunity and triggers for adaptive immune responses. IPCs play important roles in the pathogenesis of systemic lupus erythematosus (SLE) and in modulating immune responses after hematopoietic cell transplantation. Understanding IPC development from hematopoietic progenitor cells (HPCs) may provide critical information in controlling viral infection, autoimmune SLE and graft-versus-host disease. FLT3-ligand (FLT3-L) represents a key IPC differentiation factor from HPCs. Although hematopoietic cytokines such as IL-3, IL-7, SCF, M-CSF, and GM-CSF promote expansion of CD34+ HPC in FLT3-L culture, they strongly inhibit HPCs differentiation into IPCs. Here we show that Thrombopoietin (TPO) cooperates with FLT3-L inducing CD34+ HPCs to undergo a 400 fold expansion in cell numbers and generate more than 6 x 106 IPCs per 106 CD34+ HPCs within 30 days in culture. IPCs derived from HPCs in FLT3-L/TPO cultures display blood IPC phenotype and have the capacity to produce large amounts of IFN- and differentiate into mature DCs. This culture system combined with the use of adult peripheral blood CD34+ HPCs purified from G-CSF-mobilized donors permit the generation of over 109 IPCs from a single blood donor. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Thrombopoietin and the mysteries of plasmacytoid dendritic cells Claudio Anasetti Blood 2004 103: 2433. [Full Text] [PDF] This article has been cited by other articles: Y. Huang, I. J. Fugier-Vivier, T. Miller, M. J. Elliott, H. Xu, L. D. Bozulic, P. M. Chilton, and S. T. Ildstad Plasmacytoid Precursor Dendritic Cells From NOD Mice Exhibit Impaired Function: Are They a Component of Diabetes Pathogenesis? Diabetes, September 1, 2008; 57(9): 2360 - 2370. [Abstract] [Full Text] [PDF] K. Li, R. Y. T. Sung, W. Z. Huang, M. Yang, N. H. Pong, S. M. Lee, W. Y. Chan, H. Zhao, M. Y. To, T. F. Fok, et al. Thrombopoietin Protects Against In Vitro and In Vivo Cardiotoxicity Induced by Doxorubicin Circulation, May 9, 2006; 113(18): 2211 - 2220. [Abstract] [Full Text] [PDF] A. Olivier, E. Lauret, P. Gonin, and A. 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