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Arthur Liesz – Stroke-Immunology

  • We are interested in the interplay between the brain and the immune system after stroke. Acute brain lesions disturb the well-balanced interconnection between both systems. Hence, our research focuses on both directions of brain-immune interaction: The impact of immune mechanisms on neuronal damage and recovery and the systemic immunomodulation after stroke.

    Our methodological spectrum covers diverse brain ischemia models, transgenic animal models, a broad spectrum of cutting-edge immunological techniques as well as histological, biomolecular and behavioral analysis tools. The lab has a strong translational research focus with the ultimate goal to develop novel diagnostic tools, therapies and mechanistic insights on the highly complex disease which stroke represents.

    Currently, the laboratory focuses on the following main research topics within the area of brain-immune interaction:

    Cerebral lymphocyte invasion: beyond the vasculature

    One focus of our research is the migration of pro-inflammatory leukocytes to the ischemic brain (Brain, 2011). We are investigating pathophysiological mechanisms of leukocyte-endothelial interaction and novel therapeutic approaches for translational use (Science Translational Medicine, 2015). We have previously identified the choroid plexus as a previously unrecognized invasion pathways (Acta Neuropathologica, 2017) and are further striving to understand the differential role of alternative invasion routes to the injured brain.

    An alarmin(g) consequence of stroke: Brain-released alarmins and sterile inflammation

    A third research area investigates alarmin-driven mechanisms of peripheral immune alterations after brain ischemia. We aim to characterize alarmins—humoral mediators released by the necrotic brain tissue—as modulators of the systemic immune system (The Journal of Neuroscience, 2015). We previously described alarmins as key mediators leading to the exacerbation of vascular inflammation and atherosclerosis after stroke (Science Translational Medicine, 2018). Currently, we aim to expand our knowledge on the multicellular interaction in the systemic immune compartment after stroke and the role of circulating blood factors in modulating immune homeostasis.

    Chronic neuroinflammation: friend or foe in post-stroke recovery?

    We have recently identified that acute brain ischemia not only induces acute inflammation but results in long-lasting and profound neuroinflammation. These findings suggest either a deficiency in endogenous resolution mechanisms or a preponderance of currently unknown mechanisms driving chronic immune activation after stroke. We try to elucidate the underlying mechanism and study how chronic neuroinflammation affect the chronic recovery after stroke.

    From mouse to patient … and back

    A premise of our work is to address key unmet needs of stroke patients and make use of translationally relevant tools. For this we strive to constantly improve the translational relevance of our work by standardization, performing validation trials and close interaction with clinician-scientists. Access to stroke patients allows us to identify clinically relevant questions and utilize patient biosamples and clinical data together with our experimental models to answer these questions. Currently, we are working with human blood, brain, feces and CSF samples in order to study brain-immune interactions after stroke.