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 in health and multiple sclerosis.”
Time: Wednesday December 20, 5:15 p.m.
Place: Online at zoom. For more details, please contact sarah.khalil@ukmuenster.de.
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 zoom. For more details, please contact sarah.khalil@ukmuenster.de.
© Ann-Katrin Wienkamp / Rossaint Lab, UKM Anesthesiology
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, CareerS and Cells in Motion. More information
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”. A photo gallery with impressions from the conference can be found here.
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.
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. She investigates the extracellular matrix (ECM) of blood vessels, especially those of the brain. These vessels are impermeable to cells, toxins, and pathogens and are part of the blood-brain barrier (BBB). One of Lydia Sorokin’s most important projects deals with multiple sclerosis and the question of how leukocytes penetrate the brain via the BBB in this disease, thereby causing disease symptoms. The focus is on a particular space discovered by the Sorokin team that surrounds the cerebral blood vessels and is formed by structures of the ECM. This is a favourite residence of leukocytes before they enter the brain in inflammatory brain diseases. The aim of the ERC grant-funded project is to investigate the molecular processes that are required to maintain the BBB, but allow immune cells to penetrate this barrier. To this end, Lydia Sorokin and her team want to reproduce the essential components of the BBB in vitro in three dimensions. Combined with studies on genetically modified mice, the researchers want to find out how the leukocytes manage to penetrate the brain in inflammatory diseases. The replication of the BBB in the laboratory will allow for testing of different substances in order to develop novel drugs against inflammation or tumours in the brain.
The “Advanced Grants” funding line is aimed at established scientists, who have produced outstanding scientific work over the past ten years.
Prof. Luisa Klotz and Marie Liebmann analysed the immune metabolism of cells. (Photo: Anna-Lena Börsch)
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 of individual cell types differs. It is not surprising that in recent years metabolic immune cell disorders have been observed in connection with several autoimmune diseases, including multiple sclerosis. Now scientists of the transregional collaborative research centre (CRC) 128 have demonstrated: the effectiveness of one particular multiple sclerosis drug is due to its direct interference with cell metabolism. And this is only part of the story: the active ingredient under investigation, dimethyl fumarate (DMF), has a variable effect – depending on how the cells of individual patients metabolize it.
DMF is an approved substance for therapy of relapsing-remitting multiple sclerosis (MS) and reduces the excessive immune reactions in the body. It is known to induce cell death (apoptosis) in immune cells that trigger excessive responses. “It was clear to us that cell death occurs as a result of this drug, but we did not know how,” says Marie Liebmann, a research associate in Prof. Luisa Klotz’s group at the University Hospital for Neurology in Münster. Now it has been proven: The drug specifically targets cells that convert a high amount of energy and thus produce a lot of oxygen. Through a reaction, it leads to even more oxygen being produced, which accumulates in the mitochondria, the powerplants of the cell. This oxygen, however, is highly reactive, putting the cells under high oxidative stress, which eventually kickstarts apoptosis. This type of stress, and even cell death, is to a certain extent desired by nature to enable cell activation.
The mechanism becomes problematic only when it does not happen to the desired extent. In patients with average immune metabolism, just enough cells are killed to maintain a normal immune response. In patients with low cell metabolism, there is the risk of too many T cells dying: leaving immune defenses weakened and infections becoming more likely. This so-called lymphopenia – a drop in T cell count – is a known side effect of DMF and many other drugs used to treat autoimmunity. If the cell counts drop below a certain threshold, therapy must be interrupted as the risk of infection becomes too high. In most cases, the excessive immune response plus inflammation and symptoms of the autoimmune disease will then return.
The latest research from the Münster team – made possible in part by support from the CRC 128 and the Competence Network Multiple Sclerosis – could aid better risk assessment: “We can determine patients’ cell metabolism on an individual level and thus check whether this side effect is likely,” Prof. Klotz explains, who works as a senior physician in the Department of Neurology. “But this is just the beginning,” she says since DMF is not the only drug that works differently in different patients. Already some time ago, Prof. Klotz’s team could prove similar mechanisms underlying multiple sclerosis therapy with the active ingredient teriflunomide. “It is certainly worthwhile to identify cell metabolism types in multiple sclerosis patients to be able to offer individual patient-level treatment,” Prof. Klotz adds looking towards future needs.
Reference:
Liebmann M, Korn L, Janoschka C, Albrecht S, Lauks S, Herrmann AM, Schulte-Mecklenbeck A, Schwab N, Schneider-Hohendorf T, Eveslage M, Wildemann B, Luessi F, Schmidt S, Diebold M, Bittner S, Gross CC, Kovac S, Zipp F, Derfuss T, Kuhlmann T, König S, Meuth SG, Wiendl H, Klotz L. 2021. Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity. Brain. 144(10):3126-3141.
A close interaction between gut immune responses and distant organ-specific autoimmunity including the CNS in multiple sclerosis has been established in recent years. This so-called gut-CNS axis can be shaped by dietary factors, either directly or via indirect modulation of the gut microbiome and its metabolites. Here, SFB 128 PI Luisa Klotz and colleagues report that dietary supplementation with conjugated linoleic acid, a mixture of linoleic acid isomers, ameliorates CNS autoimmunity in a spontaneous mouse model of multiple sclerosis, accompanied by an attenuation of intestinal barrier dysfunction and inflammation as well as an increase in intestinal myeloid-derived suppressor-like cells. More . . .
BioNTech SE (Nasdaq: BNTX, “BioNTech” or “the Company”) announced the publication of preclinical data on its novel mRNA vaccine approach against autoimmune diseases in the peer-reviewed journal Science. The publication titled “A non-inflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis” co-authored by SFB principal investigator Ari Waisman summarizes the findings on the disease-suppressing effects of a non-inflammatory, nucleoside-modified mRNA vaccine in several clinically relevant mouse models of multiple sclerosis (MS). More . . .
Patients suffering from COVID-19 can develop concomitant and long-term symptoms in their nervous system. The most common symptom in this context is the loss of the sense of smell and taste, while more severe symptoms such as stroke, cerebral seizures, or meningitis are possible. A team of scientists from the medical faculties at the Universities of Münster and Duisburg-Essen investigated this phenomenon, termed Neuro-COVID. They could demonstrate that immune and interferon responses are weakened in COVID-19 patients. These results were recently published in the journal Immunity.
The research teams applied state-of-the-art single-cell transcription technologies, which help visualize the expression of thousands of genes on a single-cell level. “This allowed us to characterize in detail the immune response of Neuro-COVID in the cerebral fluid at a location near the brain”, says PD Dr. Gerd Meyer zu Hörste, a senior physician in the Department of Neurology at the University Hospital Münster and senior author of the study publication. “From a group of 102 COVID-19 patients, we identified those who developed neurological symptoms and required a cerebral fluid extraction for further diagnosis”, says PD Dr. Dr. Mark Stettner, who is a senior physician in the Depart
Priv.-Doz. Dr-Gerd Meyer zu Hörste (left) and Dr. Michael Heming investigated “Neuro-Covid”.
ment of Neurology at the University Hospital Essen and led the study together with Meyer zu Hörste.
Samples from eight Neuro-COVID patients were collected and sent to Münster for analysis. “An increased number of T cells in the patients’ cerebral fluid had reached a stage of exhaustion”, says Dr. Michael Heming, first author of the study and assistant physician in the Department of Neurology at the University Hospital Münster. Also, the interferon answer of Neuro-COVID patients was reduced compared with viral brain inflammation. Interferons are an essential early defense mechanism for viral diseases. The researchers further found an increased number of dedifferentiated phagocytes in the cerebral fluid.
“These findings indicate a reduced antiviral immune response in Neuro-COVID patients”, says Prof. Christoph Kleinschnitz, Director of the Department of Neurology at the University Hospital Essen. A more detailed understanding of the Neuro-COVID phenomenon is the basis for faster disease detection and improved treatment. “Publication of the study results in a high-class journal such as Immunity is the result of intensive and hard work. Our researchers achieved impressive results within a short time”, says Prof. Wiendl, Director of the Department of Neurology at the University Hospital Münster.