The regulation of immune homeostasis
requires precise communication between cells of the innate and adaptive immune
systems. Dysregulation in components of both types of cellular immunity can
lead to a variety of pathological conditions that range from immune
deficiencies to chronic activation of the innate immune response.
The
“cross-talk” between the adaptive and innate immune systems is mediated by
hematopoietic growth and survival factors, commonly termed cytokines. Cytokines
direct cells of the immune system through interaction with their cognate
receptors on the surface of effector cells. Interaction of ligand and receptor
leads to activation of a plethora of intracellular signalling molecules,
resulting in the initiation of a complex program of events modifying cellular
function. Any imbalance in the levels of these cytokines, or perturbation in
receptor-induced intracellular signalling, can have severe consequences for
immune homeostasis.
Of particular importance for the tight control of immune
function is the presence and role regulatory T cells (Treg) in inflammatory
diseases and the interaction between innate and adaptive immunity in guiding
tolerance. It is recently become apparent that Treg cells may be crucial
targets in the development of novel strategies for the treatment of
(auto)immune diseases.
This program applies both a bench-to-bedside
and bedside-to-bench approach, which has lead to development and application of
experimental disease models (see below).
General Aims
1. To understand the cellular and molecular
mechanisms controlling the functioning of a normal and productive adaptive and
innate immune system.
2. To identify specific (molecular) mechanisms
underlying dysregulation of these processes that can lead to both hypo- and
hyper-reactive immunity.
3. To develop new technologies
to manipulate primary innate immune cells, thereby providing the necessary
bridge between fundamental and clinical research.