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

Wed, 23/08/2023
Neurology Webinar on human brain T cells in health and multiple sclerosis
Muenster. The SFB 128 is happy welcome Joost J.F.M. Smolders, MD, PhD , head of MS Center ErasMS and Neuroimmunology Brain (NIB) Research Group at the Department of Immunology of the Erasmus University Medical Center (Erasmus MC), as lecturer at the Muenster Neurology Webinar. His talk is entitled “Unique features of human brain T cells […]...more
Thu, 03/08/2023
Neurology Webinar – How much gut needs the brain
Muenster. In December 2023, Prof. Anne-Katrin Pröbstel, Head of the Interdisciplinary Autoimmune Clinic at the University Hospital of Basel, will visit Muenster to give insights into the microbiota-immune crosstalk in neuroonflammation. Her presentation – which ois part of the Muenster Neurology Webinar – will be live-streamed. Time: Wednesday, December 13, 5:15 p.m. Place: Online at […]...more
Thu, 02/02/2023
3rd Inflammation & Imaging Symposium in Münster, 11-13 September 2023
Application has opened! We cordially invite you to join this international conference and discuss the latest developments in research on inflammation and the imaging of the immune system with us. The symposium is organised by eight research networks from the University of Münster – CRU 342, CRC 1009, CRC 1450, CRC/TR 128, CRC/TR 332, InFlame, […]...more