Hepatic stellate cells mediate differentiation of dendritic cells from monocytes.

BACKGROUND We have previously reported that human umbilical cord blood (UCB)-nucleated cells differentiate into hepatocyte-like cells when cultured in a 5-cytokine cocktail medium. We further found that UCB cells rather differentiated into dendritic-shaped cells by coculture with a human stellate cell (HSC) line, LI90. METHODS Monocytes from UCB and adult peripheral blood were cocultured with LI90 or rat primary HSCs in a cell-culture insert. Monocytes were also cultured with LI90-conditioned medium containing secreted factors, which were analyzed by a cytokine array. RESULTS In the coculture with LI90, resulting dendritic-shaped cells from monocytes expressed dendritic cell (DC) markers and activated allogeneic T cells, indicating that the dendritic-shaped cells were DCs. LI90 in the cytokine cocktail medium secreted various inflammatory factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4. Fibroblast growth factor-2 in the cytokine cocktail was responsible for GM-CSF production from LI90 cells and for differentiation of monocytes into DCs in the LI90 coculture. Moreover, the coculture of monocytes with activated HSCs derived from damaged rat liver induced the differentiation of DCs, whereas quiescent HSCs derived from normal liver scarcely induced such a change. CONCLUSION These results suggest that activated HSCs are involved in differentiation of monocytes into DCs in the liver.

[1]  C. Guguen-Guillouzo,et al.  Hepatic environment elicits monocyte differentiation into a dendritic cell subset directing Th2 response. , 2006, Journal of hepatology.

[2]  V. P. Eswarakumar,et al.  Cellular signaling by fibroblast growth factor receptors. , 2005, Cytokine & growth factor reviews.

[3]  D. Brenner,et al.  Erratum: Liver fibrosis (Journal of Clinical Investigation (2005) 115 (209-218) DOI:10.1172/JCI200524282) , 2005 .

[4]  C. Gandhi,et al.  Inhibition of T‐cell responses by hepatic stellate cells via B7‐H1–mediated T‐cell apoptosis in mice , 2004, Hepatology.

[5]  R. DeMatteo,et al.  GM‐CSF expands dendritic cells and their progenitors in mouse liver , 2003, Hepatology.

[6]  A. Lau,et al.  Dendritic cells and immune regulation in the liver , 2003, Gut.

[7]  K. Yoshizato,et al.  Pleiotrophin/heparin-binding growth-associated molecule as a mitogen of rat hepatocytes and its role in regeneration and development of liver. , 2002, The American journal of pathology.

[8]  O. Leo,et al.  T Cell-Dependent Maturation of Dendritic Cells in Response to Bacterial Superantigens1 , 2002, The Journal of Immunology.

[9]  T. Irimura,et al.  Kupffer cell-mediated recruitment of rat dendritic cells to the liver: roles of N-acetylgalactosamine-specific sugar receptors. , 2001, Gastroenterology.

[10]  P. Wernet,et al.  Phenotypic and functional comparison of monocytes from cord blood and granulocyte colony-stimulating factor-mobilized apheresis products. , 2001, Experimental hematology.

[11]  A Geerts,et al.  History, Heterogeneity, Developmental Biology, and Functions of Quiescent Hepatic Stellate Cells , 2001, Seminars in liver disease.

[12]  F. Marra,et al.  Cytokine Receptors and Signaling in Hepatic Stellate Cells , 2001, Seminars in liver disease.

[13]  N. Kawada,et al.  Inhibition of hepatic stellate cell proliferation and activation by the semisynthetic analogue of fumagillin TNP‐470 in rats , 2000, Hepatology.

[14]  F. Marumo,et al.  Expression of C-C Chemokines is Associated with Portal and Periportal Inflammation in the Liver of Patients with Chronic Hepatitis C , 2000, Laboratory Investigation.

[15]  C. Basilico,et al.  Compensation by Fibroblast Growth Factor 1 (FGF1) Does Not Account for the Mild Phenotypic Defects Observed in FGF2 Null Mice , 2000, Molecular and Cellular Biology.

[16]  Xiaochong Wu,et al.  Specificity for Fibroblast Growth Factors Determined by Heparan Sulfate in a Binary Complex with the Receptor Kinase* , 1999, The Journal of Biological Chemistry.

[17]  K. Tadokoro,et al.  Interleukin-13 is involved in functional maturation of human peripheral blood monocyte-derived dendritic cells. , 1999, Experimental hematology.

[18]  K. Wake,et al.  Maturation of rat dendritic cells during intrahepatic translocation evaluated using monoclonal antibodies and electron microscopy , 1998, Cell and Tissue Research.

[19]  R. Steinman,et al.  Dendritic cells and the control of immunity , 1998, Nature.

[20]  H. Klocker,et al.  Prostaglandin E2 and Tumor Necrosis Factor ␣ Cooperate to Activate Human Dendritic Cells: Synergistic Activation of Interleukin 12 Production , 1997 .

[21]  T. Ezaki,et al.  A Novel Migration Pathway for Rat Dendritic Cells from the Blood: Hepatic Sinusoids–Lymph Translocation , 1997, The Journal of experimental medicine.

[22]  M. Minemura,et al.  Expression and localization of basic fibroblast growth factor (bFGF) in the repair process of rat liver injury. , 1996, Journal of hepatology.

[23]  Y. Baruch,et al.  Basic fibroblast growth factor is hepatotropic for rat liver in regeneration. , 1995, Journal of hepatology.

[24]  T. Masuda,et al.  Establishment of a new human cell line, LI90, exhibiting characteristics of hepatic Ito (fat-storing) cells. , 1995, Laboratory investigation; a journal of technical methods and pathology.

[25]  M. Tsurudome,et al.  Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes. Induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies. , 1994, Journal of immunology.

[26]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[27]  N. Kawada,et al.  The contraction of hepatic stellate (Ito) cells stimulated with vasoactive substances. Possible involvement of endothelin 1 and nitric oxide in the regulation of the sinusoidal tonus. , 1993, European journal of biochemistry.

[28]  R. Steinman,et al.  Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor , 1992, The Journal of experimental medicine.

[29]  S. Kaufmann,et al.  Ito cells are liver-resident antigen-presenting cells for activating T cell responses. , 2007, Immunity.

[30]  R. Bataller,et al.  Amendment history : Corrigendum ( April 2005 ) Liver fibrosis Ramón Bataller , 2018 .

[31]  柿沼 晴 Human umbilical cord blood as a source of transplantable hepatic progenitor cells , 2003 .

[32]  I. N. Crispe,et al.  Hepatic T cells and liver tolerance , 2003, Nature Reviews Immunology.

[33]  P. Allavena,et al.  Interleukin-10 increases mannose receptor expression and endocytic activity in monocyte-derived dendritic cells , 1998, International journal of clinical & laboratory research.

[34]  田端 信忠 Expression of fusion regulatory proteins (FRPs) on human peripheral blood monocytes : induction of homotypic cell aggregation and formation of multinucleated giant cells by anti-FRP-1 monoclonal antibodies , 1995 .

[35]  K. Wake Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. , 1980, International review of cytology.