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Blood, 1 July 2006, Vol. 108, No. 1, pp. 218-227. Prepublished online as a Blood First Edition Paper on March 9, 2006; DOI 10.1182/blood-2005-08-3141. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: 2005-08-3141v1 108/1/218    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 Rutella, S. Articles by Lemoli, R. M. Search for Related Content PubMed PubMed Citation Articles by Rutella, S. Articles by Lemoli, R. M. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features Sergio Rutella, Giuseppina Bonanno, Annabella Procoli, Andrea Mariotti, Daniela G. de Ritis, Antonio Curti, Silvio Danese, Gloria Pessina, Simona Pandolfi, Federica Natoni, Annalaura Di Febo, Giovanni Scambia, Rossella Manfredini, Simona Salati, Sergio Ferrari, Luca Pierelli, Giuseppe Leone, and Roberto M. Lemoli Departments of Hematology, Gynecology and Obstetrics, Catholic University Medical School, Rome; Institute of Hematology and Medical Oncology "L.&A. Seràgnoli," University of Bologna, Bologna; Stem Cell Research Center, S. Orsola-Malpighi Hospital, Bologna; Polo Biomedico, Azienzia Sanitaria Locale (ASL) Viterbo/Università della Tuscia (UNITUS), Viterbo; Department of Gastroenterology, Instituto Clinico Humanitas, Rozzano, Milan; and the Department of Biomedical Sciences, University of Modena and Reggio Emilia, Italy. Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-1 (TGF-1), promote the differentiation of tolerogenic dendritic cells (DCs). Hepatocyte growth factor (HGF) is a pleiotropic cytokine whose effects on human DC differentiation and function have not been investigated. Monocytes cultured with HGF (HGFMo) differentiated into accessory cells with DC-like morphology, released low amounts of IL-12p70 and up-regulated IL-10 both at the mRNA and at the protein level. Upon activation with HGFMo, allogeneic CD4+CD25- T cells expressed the T regulatory (Treg)-associated transcription factor FoxP3, proliferated poorly, and released high levels of IL-10. Interestingly, blockade of surface immunoglobulin-like transcript 3 (ILT3) on HGFMo or neutralization of secreted IL-10 translated into partial restoration of T-cell proliferation. Secondary stimulation of HGFMo-primed CD4+ T cells with immunogenic DCs differentiated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 from monocytes of the same donor resulted in measurable T-cell proliferation. HGFMo-primed CD4+ T cells significantly inhibited the proliferation of naive CD4+CD25- T cells in a cell-contact-dependent manner. Finally, DNA microarray analysis revealed a unique gene-expression profile of HGF-activated monocytes. Collectively, our findings point to a novel role for HGF in the regulation of monocyte/DC functions that might be exploited therapeutically. 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