Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1), 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.

Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features / Rutella, S; Bonanno, G; Procoli, A; Mariotti, A; de Ritis, Dg; Curti, A; Danese, S; Pessina, G; Pandolfi, S; Natoni, F; Di Febo, A; Scambia, G; Manfredini, Rossella; Salati, Simona; Ferrari, Sergio; Pierelli, L; Leone, G; Lemoli, R. M.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 108:(2006), pp. 218-227.

Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features.

MANFREDINI, Rossella;SALATI, Simona;FERRARI, Sergio;
2006

Abstract

Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-beta1 (TGF-beta1), 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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Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features / Rutella, S; Bonanno, G; Procoli, A; Mariotti, A; de Ritis, Dg; Curti, A; Danese, S; Pessina, G; Pandolfi, S; Natoni, F; Di Febo, A; Scambia, G; Manfredini, Rossella; Salati, Simona; Ferrari, Sergio; Pierelli, L; Leone, G; Lemoli, R. M.. - In: BLOOD. - ISSN 0006-4971. - STAMPA. - 108:(2006), pp. 218-227.
Rutella, S; Bonanno, G; Procoli, A; Mariotti, A; de Ritis, Dg; Curti, A; Danese, S; Pessina, G; Pandolfi, S; Natoni, F; Di Febo, A; Scambia, G; Manfredini, Rossella; Salati, Simona; Ferrari, Sergio; Pierelli, L; Leone, G; Lemoli, R. M.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/708156
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