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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1189-1197. Prepublished online as a Blood First Edition Paper on April 20, 2006; DOI 10.1182/blood-2006-01-007187. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2006-01-007187v1 108/4/1189    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Tang, H. Articles by Cao, X. Search for Related Content PubMed PubMed Citation Articles by Tang, H. Articles by Cao, X. Related Collections Hematopoiesis and Stem Cells Hemostasis, Thrombosis, and Vascular Biology Stem Cells in Hematology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Endothelial stroma programs hematopoietic stem cells to differentiate into regulatory dendritic cells through IL-10 Hua Tang, Zhenhong Guo, Minghui Zhang, Jianli Wang, Guoyou Chen, and Xuetao Cao From the Institute of Immunology, Zhejiang University, Hangzhou, PR China; and the Institute of Immunology, Second Military Medical University, Shanghai, PR China. Regulatory dendritic cells (DCs) have been reported recently, but their origin is poorly understood. Our previous study demonstrated that splenic stroma can drive mature DCs to proliferate and differentiate into regulatory DCs, and their natural counterpart with similar regulatory function in normal spleens has been identified. Considering that the spleen microenvironment supports hematopoiesis and that hematopoietic stem cells (HSCs) are found in spleens of adult mice, we wondered whether splenic microenvironment could differentiate HSCs into regulatory DCs. In this report, we demonstrate that endothelial splenic stroma induce HSCs to differentiate into a distinct regulatory DC subset with high expression of CD11b but low expression of Ia. CD11bhiIalo DCs secreting high levels of TGF-, IL-10, and NO can suppress T-cell proliferation both in vitro and in vivo. Furthermore, CD11bhiIalo DCs have the ability to potently suppress allo-DTH in vivo, indicating their preventive or therapeutic perspectives for some immunologic disorders. The inhibitory function of CD11bhiIalo DCs is mediated through NO but not through induction of regulatory T (Treg) cells or T-cell anergy. IL-10, which is secreted by endothelial splenic stroma, plays a critical role in the differentiation of the regulatory CD11bhiIalo DCs from HSCs. These results suggest that splenic microenvironment may physiologically induce regulatory DC differentiation in situ. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Zhang, S. Liu, P. Yang, C. Han, J. Wang, J. Liu, Y. Han, Y. Yu, and X. Cao Fibronectin maintains survival of mouse natural killer (NK) cells via CD11b/Src/{beta}-catenin pathway Blood, November 5, 2009; 114(19): 4081 - 4088. [Abstract] [Full Text] [PDF] S. Takenaka, S. McCormick, E. Safroneeva, Z. Xing, and J. Gauldie Influence of the Tissue Microenvironment on Toll-Like Receptor Expression by CD11c+ Antigen-Presenting Cells Isolated from Mucosal Tissues Clin. Vaccine Immunol., November 1, 2009; 16(11): 1615 - 1623. [Abstract] [Full Text] [PDF] Q. Liu, C. Zhang, A. Sun, Y. Zheng, L. 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