Balancing glutamate and cation channel signaling in inflammatory neuronal injury

B12

In the previous funding period, we identified a novel β1-integrin/Kv1.3-mediated vesicular glutamate release pathway in Th17 cells inducing local cytoplasmatic calcium release and subsequent dam-age in neurons (Birkner et al., JCI 2019). The aim of this funding period is to i) achieve a deeper mechanistic understanding of this novel pathway and – in line with the overal goal of this third CRC funding – to ii) work on bringing the concept towards a human translation.
Specifically, we will explore possible autocrine and paracrine T cell signaling pathways, as well as the balance between two glutamate release pathways and their relation with T cell subsets and pathogenicity. Next, we will assess the impact of direct T cell-neuron interaction on neuronal calcium homeostasis and functional behaviour making use of all optical in vivo approaches. Finally, we could already show that Th17 cells derived from MS patients have a higher production of glutamate and this is linked to higher glutamine levels in the CSF of MS patients compared to control patients. In the EAE mouse model, intrathecal application of a glutaminase inhibitor reduces clinical symptoms. With support of the Z02 platform, we aim to correlate glutamate-pathway specific data with specific clinical phenotypes.
Blood Brain Barrier

Principal Investigator:

Prof. Dr. med. Stefan Bittner
Klinik für Neurologie, Forschungszentrum für Immuntherapie
Mainz
stefan.bittner@unimedizin-mainz.de

News

Tue, 28/06/2022
CRC Retreat in Münster
Muenster. After a long pause, more than 90 participants of the CRC joined in Muenster Factory Hotel to update on the latest developments. We heard the most recent on a selection of the CRC projects and there was also plenty of time for fruitful discussion and socializing in the evening....more
Mon, 23/05/2022
EU Research Council awards Lydia Sorokin Advanced Grant
Münster – The biochemist and Principal investigator of the CRC 128 Prof. Dr. Lydia Sorokin has received the coveted “Advanced Grant” awarded by the European Research Council (ERC). The funding of ca. 2.3 million euros enables the realisation of outstanding research projects. Lydia Sorokin heads the Institute for Physiological Chemistry and Pathobiochemistry at Muenster University. […]...more
Wed, 19/01/2022
One drug – different effects: Metabolism of immune cells influences mode of action and could be an indicator for side effects
Muenster – One person can eat large amounts of pasta and still be a small dress size while another looks at a piece of chocolate and puts on weight: metabolism varies between individuals – and this goes beyond a subjective feeling. What is apparent in the overall organism also applies to each cell: the metabolism […]...more