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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3175-3185. Prepublished online as a Blood First Edition Paper on July 30, 2008; DOI 10.1182/blood-2008-05-159921. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-05-159921v1 112/8/3175    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 Xia, S. Articles by Cao, X. Search for Related Content PubMed PubMed Citation Articles by Xia, S. Articles by Cao, X. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 27, 2008 Accepted July 9, 2008 Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells maintaining liver tolerance Sheng Xia, Zhenhong Guo, Xiongfei Xu, Hai Yi, Quanxing Wang, and Xuetao Cao* National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai, China Institute of Immunology, Zhejiang University, Hangzhou, China * Corresponding author; email: caoxt{at}public3.sta.net.cn. Liver has been generally considered as an organ prone to tolerance induction and maintenance. However, whether and how the unique liver microenvironment contributes to tolerance maintenance is largely unknown. Here we used liver fibroblastic stromal cells to mimic the liver microenvironment and found that liver stroma could induce Lin-CD117+ progenitors to differentiate into dendritic cells (DCs) with low CD11c, MHC II but high CD11b expression, high IL-10 but low IL-12 secretion. Such regulatory DCs could inhibit T cell proliferation in vitro and in vivo, induce apoptosis of the activated T cells and alleviate the damage of autoimmune hepatitis. Furthermore, liver stroma-derived M-CSF was found to contribute to the generation of such regulatory DCs. Regulatory DC-derived PGE2 and T cell-derived IFN-gamma were responsible for the regulatory function. Natural counterpart of regulatory DCs was phenotypically and functionally identified in the liver. Importantly, Lin-CD117+ progenitors could be differentiated into regulatory DCs in liver once transferred into liver. Infusion with liver regulatory DCs alleviated experimental autoimmune hepatitis. Therefore, we demonstrate that the liver microenvironment is highly important to program progenitors to differentiate into regulatory DCs in situ, which contributes to maintenance of liver tolerance. 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] 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. Immunol., May 15, 2009; 182(10): 6207 - 6216. [Abstract] [Full Text] [PDF] D. S. Game, X. Cao, and S. Jiang Regulatory T Cells: The Cunning Fox and Its Clinical Application Sci. Signal., December 23, 2008; 1(51): mr3 - mr3. [Abstract] [Full Text] [PDF]

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