The main interest of our group is the understanding of (patho-)physiological mechanisms underlying the crosstalk between the immune and central nervous systems (CNS). These complex and dynamic interactions are especially relevant in autoimmune diseases of the CNS such as multiple sclerosis (MS). Using broad technical expertise ranging from molecular biological, immunological and electrophysiological methods to animal experiments in disease models and blood and tissue samples from patients with MS, we are specifically interested in:
Ion channels are ubiquitous signal integrators regulating basic cellular functions mandatory for key pathways in autoinflammatory conditions such as immune cell activation, effector functions, demyelination and neuronal cell death. Our main interest lies in the specific role of potassium channels such as two-pore Domain (K2P) channels for regulating key pathways in autoimmunity.
Migration of immune cells into the CNS tissue is a multi-step process dependent on an interaction between leukocytes and endothelial cells of the blood-brain barrier. We, among others, have discovered that KCNK2, a member of the K2P channel family, regulates the inflammatory phenotype of endothelial cells opening up novel research directions on the blood-brain barrier.
Two-photon live imaging is a powerful tool to visualize pathological pathways directly in CNS lesions. This approach allows novel insights into the dynamic communication of immune, glial and neuronal cells within the inflamed tissue micromilieu. We, among others, have identified i) a novel pathway of neuronal damage mediated by Th17 cell-derived glutamate, and ii) a beneficial side of CNS myeloid cells that are able to capture and engulf invading T cells thereby counteracting autoinflammation.
The therapeutic landscape of MS is rapidly evolving due to the development of novel, highly specific immunomodulatory therapies. An optimal stratification of MS patients is still challenging due to heterogenic disease courses and therapy responses. We explore emerging biomarkers indicating disease activitiy and neurodegenerative processes such as neurofilament light chains as a marker of axonal damage in MS patients.
Our research group is part of the Focus Program Translational Neuroscience (FTN), the Research Center for Immunotherapy (FZI) and the Rhine-Main Neuroscience Network (rmn2). Our Group is funded by the Hermann and Lilly Schilling Foundation.
Bittner S, Pape K, Klotz L, Zipp F. (2023) Implications of immunometabolism for smouldering MS pathology and therapy. Nat Rev Neurol Online ahead of print.
This review summarizes the role of immune cell metabolism as driver for smouldering inflammation that is characterized by compartmentalized CNS inflammation and chronic neuronal damage in multiple sclerosis.
International Multiple Sclerosis Genetics Consortium (Bittner S as part of the IMSGC working Group) and MultipleMS Consortium. (2023) Locus for severity implicates CNS resilience in progression of multiple sclerosis. Nature Online ahead of print.
This large consortium work indentifies the first genetic determinants of multiple sclerosis progression.
Bittner S, Oh J, Havrdova EK, Tintore M, Zipp F. (2021) The potential of serum neurofilament as biomarker for multiple sclerosis. Brain 144(10):2954-2963.
This review summarizes the current Knowledge on the use of neurofilament as a biomarker for multiple sclerosis, proposes guidelines for clinical implementation and identifies current obstacles in the field.
Bittner S*, Steffen F*, Uphaus T, Muthuraman M, Fleischer V, Salmen A, Luessi F, Berthele B, Klotz L, Meuth SG, Bayas A, Paul F, Hartung H-P, Linker R, Heesen C, Stangel M, Wildemann B, Then Bergh F, Tackenberg B, Kümpfel T, Weber F, Zettl UK, Ziemann U, Tumani H, Groppa S, Mühlau M, Lukas C, Hemmer B, Wiendl H, Gold R, Zipp F, for the German Competence Network Multiple Sclerosis. (2020) Clinical implications of Serum neurofilament in newly diagnosed MS patients: a longitudinal multicenter cohort study. EBioMedicine 56: 102807. *equally contributing
This cohort study from 23 leading German MS Centers evaluates the potential of measuring serum neurofilament for diagnosis, prognosis and therapeutic stratification in >800 patients at disease onset.
Wasser B*, Luchtman D*, Löffel J, Robohm K, Birkner K, Stroh A, Vogelaar CF, Zipp F§, Bittner S§. (2020) Myeloid cells capture living CNS-invading T cells during neuroinflammation. J Exp Med 217(6): e20190812. *equally contributing, §equally contributing and corresponding.
Using two-photon live Imaging, the authors characterize previously overlooked beneficial properties of microglia in the inflamed CNS as they recognize and actively engulf invading autoreactive T lymphocytes.
Birkner K, Wasser B, Ruck T, Thalman C, Luchtman D, Pape K, Schmaul S, Bitar L, Krämers-Albers EM, Stroh A, Meuth SG, Zipp F§, Bittner S§. (2020) ß1-integrin- and Kv1.3 channel dependent signaling stimulates glutamate release from Th17 cells. J Clin Invest 130(2): 715-732. §equally contributing and corresponding
This paper unravels a novel cytotoxic pathway of Th17 cell-neuron interaction, wherein Th17 cells directly release glutamate towards inflamed neurons via a therapeutically addressable b1-integrin-Kv1.3 pathway.
Full publication list available here.
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