Ligation of CD47 during monocyte differentiation into dendritic cells results in reduced capacity for interleukin-12...

We have previously shown that the CD47-binding thrombospondin-1 (TSP-1)-derived peptide 4N1K induces a rapid apoptosis-like death of human monocytes and dendritic cells (DCs). However, not all cells were susceptible to the peptide-induced cell death and here, we have investigated whether surviving monocytes could differentiate into functionally normal DCs. We found that the cell-surface phenotype, the T-cell stimulatory capacity and the ability to undergo lipopolysaccharide (LPS)-induced maturation into CD83+ DCs were essentially identical in 4N1K-derived and control DCs. Interleukin-10 (IL-10) production was also normal, but a significant downregulation of the pro-inflammatory cytokines IL-12 and tumour necrosis factor-alpha (TNF-alpha) was observed in the 4N1K-derived DCs. To the contrary, simultaneous stimulation of control DCs with 4N1K and LPS + interferon-gamma did not alter IL-12 production. These results indicate that although activation of the TSP-1-binding region of CD47 on monocytes induces apoptosis in a large proportion of the cells, it does not hamper the overall capacity of the surviving cells to differentiate into DCs. Such DCs, however, have a reduced capacity for IL-12 and TNF-alpha production, and the possibility that this is linked to the uptake of apoptotic cells is discussed.