Natural killer (NK) cells and innate lymphoid cells (ILC) are important immune cells. NK cells are
indispensible for anti-tumor and anti-viral activities, and ILC are essential for defense against
pathogens and contribute to mucosal homeostasis. Despite their beneficial role, overproduction of
cytokines by ILC is often associated with inflammatory diseases such as Crohn's disease, asthma
and psoriasis. Furthermore, functional impairment of NK cells is observed in leukemia patients
who received hematopoietic stem cell transplantation, leading to a less favorable outcome.
Recently, this impairment has been attributed to downregulation of T-bet and Eomes in NK cells.
T-bet and Eomes are two transcription factors that play a crucial role in differentiation, maturation
and function of murine NK cells and ILC. Much less information is available for human research.
Translational research unraveling the regulatory role of T-bet and Eomes in human NK and ILC
development is essential and could offer new perspectives regarding potential therapies.
Therefore, molecular techniques are used to create loss-of-function and gain-of-function of T-bet
and Eomes in human hematopoietic stem cells, which are then cultured in an in vitro
differentiation model to evaluate the effect on development of NK cells and ILC. To gain
mechanistic insight in the role of T-bet and Eomes in NK cell and ILC development, downstream
target genes of T-bet and Eomes will also be characterized.