Neutrophils From stem cells to immune suppressors

In this thesis we established and applied different models to investigate neutrophil development in relation to effector functions in more depth. To unravel underlying mechanisms or phenotypes in neutrophil immune defects, we show in part I of this thesis the potential of iPSCs and CD34⁺ HSCs as a disease model for neutrophil development. In part II of the thesis we address the recently established – and more controversial – function of mature neutrophils as MDSCs. With our set-up to assess MDSC activity in vitro, we investigated in more depth the mechanism of the suppressive activity and whether this activity was restricted to some extent to certain developmental or (re)programmed neutrophil subsets in health or under certain disease conditions. With our set-up to assess MDSC activity in vitro, using an adapted culture system based on previous experience, it has been proven to be of immense help to identify which developmental programming or activities are key to obtain the various neutrophil-specific effector activities, including MDSC activity, as we will describe in the subsequent chapters of this thesis.