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 channel mediated regulation of immune cell and CNS functions
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.
Regulation of immune cell migration into the CNS
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.
Live imaging of inflammatory and degenerative pathways in the inflamed CNS tissue
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.
Understanding the heterogeneity of MS: Role of emerging biomarkers
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.
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
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
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
Ellwardt E*, Pramanik G*, Luchtman D, Novkovic T, Jubal ER, Vogt J, Arnoux I, Vogelaar CF, Mandal S, Schmalz M, Barger Z, Ruiz de Azua I, Kuhlmann T, Lutz B, Mittmann T, Bittner S, Zipp F§, Stroh A§. (2018) Maladaptive cortical hyperactivity upon recovery from experimental autoimmune encephalomyelitis. Nat Neurosci 21(19):1392-1403. *equally contributing, §equally contributing and corresponding
Bittner S, Zipp F. (2018) AAN unveils new Guidelines for MS disease-modifying therapy. Nat Rev Neurol 14(7): 384-386.
Bittner S, Ruck T, Schuhmann MK, Herrmann AM, Moha ou Maati H, Bobak N, Gobel K, Langhauser F, Stegner D, Ehling P, Borsotto M, Pape HC, Nieswandt B, Kleinschnitz C, Heurteaux C, Galla HJ, Budde T, Wiendl H, Meuth SG. (2013) Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS. Nat Med 19: 1161-1165.
Bittner S, Bobak N, Herrmann AM, Gobel K, Meuth P, Hohn KG, Stenner MP, Budde T, Wiendl H, Meuth SG. (2010) Upregulation of K2P5.1 potassium channels in multiple sclerosis. Ann Neurol 68: 58-69.