Granulocyte colony-stimulating factor promotes the generation of regulatory DC through induction of IL-10 and IFN-α

Sergio Rutella, Giuseppina Bonanno, Luca Pierelli, Andrea Mariotti, Ettore Capoluongo, Anna Maria Contemi, Franco Ameglio, Antonio Curti, Daniela G. de Ritis, Maria Teresa Voso, Alessandro Perillo, Salvatore Mancuso, Giovanni Scambia, Roberto M. Lemoli, Giuseppe Leone

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently demonstrated that G-CSF promotes the generation of human T regulatory (TREG) type 1 cells. In this study, we investigated whether the immunomodulatory effects of G-CSF might be mediated by DC. CD14+ monocytes were cultured with serum collected after clinical administration of G-CSF (post-G), which contained high amounts of IL-10 and IFN-α. Similar to incompletely matured DC, monocytes nurtured with post-G serum acquired a DC-like morphology, expressed high levels of costimulatory molecules and HLA-DR, and exhibited diminished IL-12p70 release and poor allostimulatory capacity. Importantly, post-G DC-like cells were insensitive to maturation stimuli. As shown by neutralization studies, IFN-α and, even more pronounced, IL-10 contained in post-G serum inhibited IL-12p70 release by post-G DC-like cells. Furthermore, phenotypic and functional features of post-G DC-like cells were replicated by culturing post-G monocytes with exogenous IL-10 and IFN-α. Post-G DC-like cells promoted Ag-specific hyporesponsiveness in naive allogeneic CD4+ T cells and orchestrated a TREG response that was dependent on secreted TGF-β1 and IL-10. Finally, neutralization of IL-10 and IFN-α contained in post-G serum translated into abrogation of the regulatory features of post-G DC-like cells. This novel mechanism of immune regulation effected by G-CSF might be therapeutically exploited for tolerance induction in autoimmune disorders.

Original languageEnglish
Pages (from-to)1291-1302
Number of pages12
JournalEuropean Journal of Immunology
Volume34
Issue number5
DOIs
Publication statusPublished - May 2004

Keywords

  • Anergy
  • Cellular differentiation
  • Cytokines
  • Dendritic cells
  • Human
  • Suppression
  • Tolerance

ASJC Scopus subject areas

  • Immunology

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