Long considered immune-privileged, rich interactions between the brain and the immune system (neuro-immune interactions) have been recently identified and shown to play important roles in physiology and disease. In neurodegenerative diseases, in particular, the impact of the immune system on disease pathogenesis and progression has recently come into focus. Understanding the interactions between the CNS and the immune system is the basis for developing novel therapeutic strategies to tackle devastating neurological diseases like Alzheimer´s disease (AD).
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A major focus of our research is microglia, the brain´s intrinsic macrophages, which play important roles in CNS development, homeostasis and as first responders to pathological events. Our work combines in vivo studies using transgenic mouse models with ex vivo experiments in cell and tissue culture that we ultimately strive to translate to the human condition through analyses of human tissue samples.
Neuro-immune interactions in AD
Research efforts in the past decade have underscored the importance of neuro-immune interactions for the pathogenesis and progression of AD. We are particularly interested in the contribution of microglia and peripheral macrophages to AD pathology. In this context, we have recently described IL-12/IL-23 signaling in resident brain cells as a valuable therapeutic target for the treatment of AD. Beyond the impact of resident brain cells, we are also exploring the influence of the peripheral immune system on cerebral Aβ pathology.
Mechanisms of immunotherapy in AD
Active and passive vaccination approaches targeting beta-Amyloid (Aβ) are promising therapeutic strategies for the treatment of AD and currently evaluated in clinical trials, despite the fact that the precise mechanism of action is not known. To get a better insight into the mechanism of Aβ-targeting immunotherapy, we are evaluating the effect of peripheral anti-Aβ antibodies on cerebral Aβ pathology ("peripheral sink") and the contribution of microglia (central effect) on the efficacy of Aβ-targeting vaccination strategies with various transgenic mouse models to aid the development of effective new treatment strategies.
Microglia physiology and pathophysiology
Well known for their role as brain macrophages, microglia comprise an ontologically distinct cell population in the CNS. While similar to peripheral tissue macrophages in many ways, recent research efforts suggest highly specialized roles of microglia in the brain that go beyond the classical notion of pro-inflammatory immune cells. With the aim of better understanding the nuanced roles of microglia in physiological and pathophysiological settings, we are investigating how microglia influence processes including hypothalamic activity, adult neurogenesis and neuropathic pain. Our goal is to gain insight into the ways in which microglia regulate the activity of neighboring cells and, in turn, how the CNS environment uniquely impacts the nature of microglia.