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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 20, 2006 Accepted March 21, 2006 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* Institute of Immunology, Zhejiang University, Hangzhou 310031, P.R.China Institute of Immunology, Second Military Medical University, Shanghai 200433, P.R.China * Corresponding author; email: caoxt{at}public3.sta.net.cn. Regulatory dendritic cells (DCs) have been reported recently, but their origin is poorly understood. Our previous study demonstrated that splenic stroma can drive mDCs to proliferate and differentiate into regulatory DCs and their natural counterpart with similar regulatory function in normal spleen is identified. Considering that spleen microenvironment supports hematopoiesis and hematopoietic stem cells (HSCs) are found in spleen of adult mice, we wonder whether splenic microenvironment could differentiate HSCs into regulatory DCs. In this report, we demonstrate that endothelial splenic stroma induces HSCs to differentiate into a distinct regulatory DCs subset which high express CD11b but low express Ia. CD11bhiIalo DCs secreting high level of TGF-[[beta]] , IL-10, 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 immunological disorders. The inhibitory function of CD11bhiIalo DCs is mediated through NO but not through induction of Treg or T cell anergy. IL-10, 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. Wang, and X. Cao Tumor-Educated CD11bhighIalow Regulatory Dendritic Cells Suppress T Cell Response through Arginase I J. 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