Systematic name M8582
Brief description Genes down-regulated in peripheral blood monocytes by CSF2RB (GM-CSF) and IL4 [GeneID=1437;3565].
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 16527888   Authors: 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 R,Salati S,Ferrari S,Pierelli L,Leone G,Lemoli RM
Exact source Table 1S: GM4-DCs vs Ctrl FC <= -1
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