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Blood, 7 May 2009, Vol. 113, No. 19, pp. 4780-4789. Prepublished online as a Blood First Edition Paper on February 19, 2009; DOI 10.1182/blood-2008-10-183145. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-10-183145v1 113/19/4780    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sato, K. Articles by Sato, K. Search for Related Content PubMed PubMed Citation Articles by Sato, K. Articles by Sato, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 7, 2008 Accepted February 8, 2009 Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease Kaori Sato, Kawori Eizumi, Tomohiro Fukaya, Shigeharu Fujita, Yumiko Sato, Hideaki Takagi, Mai Yamamoto, Naohide Yamashita, Atsushi Hijikata, Hiroshi Kitamura, Osamu Ohara, Sho Yamasaki, Takashi Saito, and Katsuaki Sato* Laboratory for Dendritic Cell Immunobiology, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan Department of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan Laboratory for Immunogenomics, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan Laboratory for Cell Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan * Corresponding author; email: katsuaki{at}rcai.riken.jp. Chronic graft-versus-host disease (cGVHD) is a limiting factor in allogeneic hematopoietic stem cell transplantation (alloHSCT) for the treatment of leukemia and other malignancies. Relative to the process that initiates and promotes cGVHD, the regulation is poorly understood. In this study, we examined the role of naturally occurring regulatory dendritic cells (DCregs) in murine major histocompatibility complex (MHC)-compatible and multiple minor histocompatibility antigen (miHAg)-incompatible model of cGVHD in alloHSCT. DCregs generated from bone marrow in vitro (BM-DCregs) exclusively expressed CD200 receptor 3 (CD200R3), which exerted a suppressive function in the Ag-specific CD4+T-cell response. CD49+CD200R3+cells showed similarities in phenotype and function to BM-DCregs, which formally distinguishes them from other leukocytes, suggesting that they are the natural counterpart of BM-DCregs. Treatment of the recipient mice following alloHSCT with the recipient-type CD49+CD200R3+cells as well as BM-DCregs protected against cGVHD, and the protection was associated with the generation of Ag-specific anergic CD4+T cells as well as CD4+CD25+Foxp3+regulatory T cells (Tregs) from donor-derived alloreactive CD4+CD25-Foxp3-T cells. In addition, the depletion of CD49+CD200R3+cells before alloHSCT enhanced the progression of cGVHD. In conclusion, CD49+CD200R3+cells act as naturally occurring DCregs to regulate the pathogenesis of cGVHD in alloHSCT mediated through the control of the transplanted alloreactive CD4+T cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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