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

Thu, 28/03/2024
Looking back and ahead: SFB/CRC 128 symposium provides new perspectives on MS research
The SFB/CRC 128 Symposium, themed “Multiple sclerosis and related disorders – past, present, and future,” unfolded on April 29th and 30th, 2024, within the historic Castle of Münster University and thus at the center of the city. This symposium garnered significant attendance and served as an exemplary forum to discuss advances in the field, present […]...more
Thu, 15/09/2022
Photo gallery: Inflammation & Imaging Symposium in the MIC building
Muenster. From September 12th to 14th scientists from Muenster University and their international guests discussed the latest developments in research on inflammation and the imaging of the immune system at the 2nd Inflammation & Imaging Symposium. The annual event is jointly organised by several research networks from Münster, among them the CRC/TRR 128 “Multiple Sclerosis”. […]...more
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