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, Roberto M. Lemoli

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Abstract

Several hematopoietic growth factors, including interleukin-10 (IL-10) and transforming growth factor-β1 (TGF-β1), 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 granulocytemacrophage 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.

Original languageEnglish
Pages (from-to)218-227
Number of pages10
JournalBlood
Volume108
Issue number1
DOIs
Publication statusPublished - Jul 1 2006

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ASJC Scopus subject areas

  • Hematology

Cite this

Rutella, S., Bonanno, G., Procoli, A., Mariotti, A., De Ritis, D. G., Curti, A., Danese, S., Pessina, G., Pandolfi, S., Natoni, F., Di Febo, A., Scambia, G., Manfredini, R., Salati, S., Ferrari, S., Pierelli, L., Leone, G., & Lemoli, R. M. (2006). Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features. Blood, 108(1), 218-227. https://doi.org/10.1182/blood-2005-08-3141