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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 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 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 Xia, S. Articles by Cao, X. Search for Related Content PubMed PubMed Citation Articles by Xia, S. Articles by Cao, X. Related Collections Hematopoiesis and Stem Cells Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Hepatic microenvironment programs hematopoietic progenitor differentiation into regulatory dendritic cells, maintaining liver tolerance Sheng Xia1,2,*, Zhenhong Guo1,*, Xiongfei Xu1, Hai Yi1, Quanxing Wang1, and Xuetao Cao1,2 1 National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, Shanghai; and 2 Institute of Immunology, Zhejiang University, Hangzhou, China The liver has been generally considered 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 macrophage colony-stimulating factor (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. The natural counterpart of regulatory DCs was phenotypically and functionally identified in the liver. Importantly, Lin–CD117+ progenitors could be differentiated into regulatory DCs in the liver once transferred into the 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 the maintenance of liver tolerance. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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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