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

NIC-News


Looking back and ahead: SFB/CRC 128 symposium provides new perspectives on MS research

Thu, 28/03/2024

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 novel research avenues and treatment strategies, and address central scientific questions and unmet clinical needs in Multiple Sclerosis (MS) and neuroimmunology.

Commencing early on Monday morning, the event attracted an audience of over 100 basic and translational scientists, many of whom have worked as members of the DFG-funded collaborative research center 128, “Multiple Sclerosis.” The symposium showcased the translation of medical research from bench to bedside, providing a comprehensive overview of the current state and future directions of research in MS and neuroimmunology through inspirational talks, engaging discussions, and poster presentations.

Frauke Zipp (Mainz) and Heinz Wiendl (Münster), the co-spokespersons of the SFB/CRC, inaugurated the symposium by examining the evolution in the MS field and its needed development in the next decade. They focused on trends such as biomarkers of disease and therapy response, enabling individualized treatment of MS in the (near) future. Then, the audience delved into neuroimmunology with Jonathan Kipnis (St. Louis), who provided new insights into brain-immune interactions at the brain’s borders. Roland Liblau (Toulouse) presented his latest work on tissue-resident T cells and the chronicity of CNS inflammatory diseases. Britta Engelhardt (Bern) outlined her novel research that is devoted to understanding the function of the different brain barriers in regulating CNS immune surveillance and how their impaired function contributes to neuroinflammatory diseases such as MS. With his talk on neuroprotection through inflammatory cytokines, Burkhard Becher (Zurich) provided insights into the latest developments in this exciting field of research.

The subsequent session on myelin, chaired by Ludia Sorokin (Münster), focused on the role of oligodendrocytes. While Martin Kerschensteiner (Munich) questioned if (and how) surviving oligodendrocytes contribute to remyelination, Tanja Kuhlmann (Münster) discussed the consequences of oligodendrocytes in MS lesions. Peter Calabresi (Baltimore) elaborated on how complement C3 defines disease-associated glial subtypes mediating neuroinflammation and neuronal pathology. Neuroinflammation leads to neuronal stress responses that contribute to neuronal dysfunction and loss. Manuel Friese (Hamburg) provided a closer look at the neuronal inflammatory stress response in MS and ways to therapeutically address it.

Vinzenz Fleischer (Mainz) opened the session on imaging in MS by examining structural brain networks and his talks was complemented by Albrecht Stroh (Mainz). Benedetta Bodini (Toulouse) shared thoughts and data about the past, current, and future role of Positron Emission Tomography (PET) imaging in MS. Alexander Flügel (Göttingen) highlighted the impact of live cell imaging on our understanding of T cell function under homeostatic and autoimmune conditions in the brain.

In the past 12 years, the CRC 128 has contributed to the careers of many young scientists. In the young investigator talk, six of them gave a concise glimpse into their specialty. Beatrice Wasser (Mainz) spoke about how interference with AMPA receptor signaling ameliorates neuroinflammation, while Lisa Richter (Munich) explained the role of IL-6 in shaping local immune milieus in the CNS. Louisa Müller-Miny (Münster) outlined how CSF flow cytometry can help diagnose and understand neuroimmunology by showing use case examples and perspectives; and Timo Uphaus (Mainz) thought outside the box by illustrating the function of the blood-brain barrier not only in neuroinflammation but also in ischemic stroke. Clara de la Rosa del Val (Munich) provided insights into essential cytokines driving macrophage phenotypes in neuroinflammation. The final talk in this session was given by Andreas Schulte-Mecklenbeck (Münster), who presented a study on immune profiling revealing that discrete cellular immune fingerprints indicate distinct disease trajectories in early MS, recently published in Science Translation Medicine.

The session on “Novel directions and technologies” was opened by chair Martin Kerschensteiner (Munich), who introduced Alexandre Prat (Montreal) who exceptionally highlighted the benefit of single-cell RNA sequencing for understanding human MS and ALS brain endothelial cells. Tobias Bopp (Mainz) elaborated on the role of metabolic communication in the development and manifestation of autoimmunity, while Gerd Meyer zu Hörste (Münster) gave an overview of his latest work studying brain borders in neuroinflammation. The integration of large data from high-throughput technologies into complex models is one of the biggest challenges for future high-tech medicine. Sergio Baranzini (San Francisco) presented solutions to this in his lecture on integrating “omics” with AI for precision medicine. With her insights into the mechanisms of action of B cell depletion therapies in MS, Jen Gommerman (Toronto) built a bridge to the sixth session of the symposium that asked, “Is there still a role for T cell immunology, or should we prioritize B cells in understanding MS?” Chair Sven Meuth (Düsseldorf) opened this second day of the symposium where the focus shifted from MS to other neuroimmunologic diseases.

In this first session of the second day, Jan Lünemann (Münster) provided an overview of his highly topical research on functional signatures of encephalitogenic antibodies in CNS autoimmune diseases. Fabienne Brilot (Sydney) examined biomarkers of a relapsing course in MOG antibody-associated disease; and Daniela Latorre (Zurich) used the example of Guillain-Barré-Syndrome to exemplify the role of autoreactive T cell immunity in human neurological autoimmune disorders. Edgar Meinl (Munich) closed the session by providing an overview of B cells and their mechanisms in neuro-immunology.

The final session, chaired by Aiden Haghikia (Magdeburg), was dedicated to learning pathogenesis via therapeutic intervention. Thomas Korn (Munich) emphasized the need for a fresh look at B cells in autoimmunity and – among other studies – presented his work on B cells in models of neuromyelitis optica spectrum disorders (NMOSD). Ari Waisman (Mainz) shared his insights on inflammatory mediators affecting blood barrier function in autoimmunity. Will cellular fingerprints help to evaluate clinical prognosis and decide on the treatment of MS? Luisa Klotz (Münster) and her team have conducted several studies on this topical question, and she discussed the main results in her talk. Naoto Kawakami (Munich) shared learnings acquired on the molecular mechanisms of T cell infiltration into the CNS with the audience. As the last speaker of this dense symposium, Nicholas Schwab (Münster) focused on reverse-translation and asked what next-generation sequencing of treatment cohorts can teach us about pathology.

Overall, all presentations reflected the enormous range of recent and ongoing MS research across the involved centers and worldwide. The principal investigators of the SFB/CRC 128 also summarized important findings from twelve years of research in this large-scale transregional DFG-funded project. Together with the distinguished guest speakers, they also gave ideas on where MS research should and will develop within the next decade.


Photo gallery: Inflammation & Imaging Symposium in the MIC building

Thu, 15/09/2022

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.


CRC Retreat in Münster

Tue, 28/06/2022

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.


EU Research Council awards Lydia Sorokin Advanced Grant

Mon, 23/05/2022

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.


One drug – different effects: Metabolism of immune cells influences mode of action and could be an indicator for side effects

Wed, 19/01/2022

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.


Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity

Mon, 09/08/2021

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 Publishes Data on Novel mRNA Vaccine Approach to Treat Autoimmune Diseases in Science

Thu, 28/01/2021

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 . . .


A new study on neurological manifestations of severe COVID-19 reveals nervous system immune deficiency

Wed, 20/01/2021

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.


Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity

Fri, 15/01/2021

It has long been acknowledged that multiple sclerosis disease risk is associated with reduced sun-exposure, and subsequent low vitamin D levels. The study by Ostkamp et al. now assessed the relationship between measures of sun exposure and MS severity. For this, the researchers analyzed data of around 2,000 patients from the German NationMS- and the French BIONAT cohort. To approximate a patients’ sunlight exposure, the researchers used serum vitamin D measurements, the geographical latitude of residence, and UV-light estimates extracted from the recordings of NASA satellites. As expected, high serum vitamin D could be shown to be associated with a reduced MS severity score, reduced risk for relapses, and lower disability accumulation over time. Furthermore, low latitude associated with higher vitamin D levels, a lower MS severity score, fewer gadolinium-enhancing lesions, and lower disability accumulation over time. As an exception, no association between latitude and disability was found in patients who were treated with IFN-β before the start of the study. This lined up with a finding from an RNA-sequencing analysis, in which the researchers could show an induction of the type I interferon-pathway in a small cohort of patients, who were treated with narrowband UVB-light for six weeks.

Patrick Ostkamp was in the team of scientists who analysed the cohort data. (Photo: Leßmann)

Therefore, as UVB potentially initiates an interferon response itself, it might be possible that no effect of UVB can be observed in patients whose blood is already saturated with interferons. Although the study shows that sunlight exposure has a beneficial effect on MS severity, the researchers argue against excessive sun exposure, as the observed effects of UV-light were of comparably low magnitude, and photosensitive patients who carried a genetic variant of the melanocortin-1-receptor (an important factor for pigmentation) even seemed to worsen upon increased sunlight exposure, according their MRI activity.

Reference: Ostkamp P, Salmen A, Pignolet B, Görlich D, Andlauer TFM, Schulte-Mecklenbeck A, Gonzalez-Escamilla G, Bucciarelli F, Gennero I, Breuer J, Antony G, Schneider-Hohendorf T, Mykicki N, Bayas A, Then Bergh F, Bittner S, Hartung H-P, Friese MA, Linker RA, Luessi F, Lehmann-Horn K, Mühlau M, Paul F, Stangel M, Tackenberg B, Tumani H, Warnke C, Weber F, Wildemann B, Zettl UK, Ziemann U, Müller-Myhsok B, Kümpfel T, Klotz L, Meuth SG, Zipp F, Hemmer B, Hohlfeld R, Brassat D, Gold R, Gross CC, Lukas C, Groppa S, Loser K, Wiendl H, Schwab N, German Competence Network Multiple Sclerosis (KKNMS) and the BIONAT Network. 2021. Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity. Proc Natl Acad Sci U S A. 118(1):e2018457118.


Transregio-Cooperative Research Centre „Multiple Sclerosis“ funded for another four years

Tue, 15/12/2020

The Collaborative Research Center 128 “Multiple Sclerosis” is entering its third round. As the German Research Association announced, the major project with locations in Münster, Mainz and Munich will be supported for a further four years (until mid-2024). Speaker Prof. Heinz Wiendl, Co-Spokesperson Prof. Frauke Zipp (Mainz) and other scientists are researching multiple sclerosis – a chronic inflammatory and neurodegenerative disease of the central nervous system. Their focus is on the interaction between the immune and nervous systems on a molecular, cellular and systems biological level. The 35 principal investigators and their teams analyse the changes in the immune system underlying the disease, effects the attack of the immune system has on the central nervous system and how these consequences can be modulated with the latest therapies. The 22 individual projects are tackling a wide range of topics, including the role of the intestinal microbiome in inflammation and nerve destruction in MS, the patterns of nerve damage that MS patients e.g. in MRI images show and the effect of various MS drugs on the immune system. In the next four years, the focus of her work will be on coping with illnesses. This means both better control and monitoring of the now widespread drugs for treating MS and translation – i.e. the transfer of research results into patient care and – the other way around – the use of knowledge from clinical practice for work in the laboratory.


Dr. Beatrice Wasser awarded DGfI Herbert Fischer Prize for Neuroimmunology

Tue, 06/10/2020

Beatrice WasserEach year, the German Society for Immunology (DGfI) recognizes young scientists who have made an outstanding contribution in the field of immunology. This year, Dr. Beatrice Wasser, a Postdoc in the group of Prof. Frauke Zipp and Prof. Stefan Bittner in the Department of Neurology, was award the Herbert Fischer Prize for Neuroimmunology for her investigation of the mechanism by which cells of the central nervous system (CNS) can control autoreactive T lymphocytes. Dr. Wasser was able to show, for the first time, that myeloid cells in the CNS can trap and kill invading pathogenic T cells. This novel defense pathway could potentially be exploited, leading to a new therapy for T cell-induced autoimmune diseases such as multiple sclerosis.

This work was recently published in the Journal of Experimental Medicine:
Wasser B, Luchtman D, Löffel J, Robohm K, Birkner K, Stroh A, Vogelaar CF, Zipp F, Bittner S. CNS-localized myeloid cells capture living invading T cells during neuroinflammation. J Exp Med 2020; 217(6): e20190812.
The official press release of the DGfI is available here.


Study with identical twins shows that the early form of multiple sclerosis has a specific pattern

Tue, 08/09/2020

Happy about the new findings from the MS-TWIN study: PhD student Claudia Janoschka (right) and group leader Prof. Luise Klotz (Photo: Deiters-Keul)

The tremendous heterogeneity of the human population presents a major obstacle in understanding how autoimmune diseases like multiple sclerosis (MS) contribute to variations in human peripheral immune signatures. To minimize heterogeneity, SFB researchers from Munich and Muenster made use of a unique cohort of 43 monozygotic twin pairs clinically discordant for MS and searched for disease-related peripheral immune signatures in a systems biology approach covering a broad range of adaptive and innate immune populations on the protein level. Results of their work were published in the latest issue of the prestigious journal PNAS.
Despite disease discordance, the immune signatures of MS-affected and unaffected cotwins were remarkably similar. Twinship alone contributed 56% of the immune variation, whereas MS explained 1 to 2% of the immune variance. Notably, distinct traits in CD4+ effector T cell subsets emerged when Lisa Ann Gerdes, Claudia Janoschka and colleagues focused on a subgroup of twins with signs of subclinical, prodromal MS in the clinically healthy cotwin. Some of these early-disease immune traits were confirmed in a second independent cohort of untreated early relapsing-remitting MS patients. Early involvement of effector T cell subsets thus points to a key role of T cells in MS disease initiation.

Adapted from.
Gerdes LA° Janoschka C°, Eveslage M, Mannig B, Wirth T, Schulte-Mecklenbeck A, Lauks S, Glau L, Gross CC, Tolosa E, Flierl-Hecht A, Ertl-Wagner B, Barkhof F, Meuth SG, Kümpfel T, Wiendl H°, Hohlfeld R*, Klotz L*. Immune signatures of prodromal multiple sclerosis in monozygotic twins. Proc Natl Acad Sci U S A 117(35):21546-21556. (°,*= equal contribution)


Breakthrough: SFB scientsists explain pathomechanism of Susac Syndrome

Mon, 09/03/2020

SFB researchers Dr. Catharina Groß, Prof. Dr. Heinz Wiendl and their team have deciphered important processes in Susac syndrome (Photo: Monecke)

Neuroinflammation is often associated with blood-brain-barrier dysfunction, which contributes to neurological tissue damage. In a paper published in the renowned journal Nature Communications SFB 128 scientists from Mueenster reveal the pathophysiology of Susac syndrome (SuS), an enigmatic neuroinflammatory disease with central nervous system (CNS) endotheliopathy. By investigating immune cells from the blood, cerebrospinal fluid, and CNS of SuS patients, Dr. Catharina Gross and her team demonstrate oligoclonal expansion of terminally differentiated activated cytotoxic CD8+ T cells (CTLs). Neuropathological data derived from both SuS patients and a newly-developed transgenic mouse model recapitulating the disease indicate that CTLs adhere to CNS microvessels in distinct areas and polarize granzyme B, which most likely results in the observed endothelial cell injury and microhemorrhages. The autors show that blocking T-cell adhesion by anti-α4 integrin-intervention ameliorates the disease in the preclinical model. Similarly, disease severity decreases in four SuS patients treated with natalizumab along with other therapy. Their study identifies CD8+ T-cell-mediated endotheliopathy as a key disease mechanism in SuS and highlights therapeutic opportunities.

Adapted from: Gross CC, Meyer C, Bhatia U, Yshii L, Kleffner I, Bauer J, Tröscher AR, Schulte-Mecklenbeck A, Herich S, Schneider-Hohendorf T, Plate H, Kuhlmann T, Schwaninger M, Brück W, Pawlitzki M, Laplaud DA, Loussouarn D, Parratt J, Barnett M, Buckland ME, Hardy TA, Reddel SW, Ringelstein M, Dörr J, Wildemann B, Kraemer M, Lassmann H, Höftberger R, Beltrán E, Dornmair K, Schwab N, Klotz L, Meuth SG, Martin-Blondel G, Wiendl H, Liblau R. CD8+ T cell-mediated endotheliopathy is a targetable mechanism of neuro-inflammation in Susac syndrome. Nat Commun. 2019 Dec 18;10(1):5779.


The brain is less immune-priviledged than we thought

Wed, 04/03/2020

Münster. Although the CNS is immune privileged, continuous search for pathogens and tumours by immune cells within the CNS is indispensable. Thus, distinct immune-cell populations also cross the blood–brain barrier independently of inflammation/under homeostatic conditions. It was previously shown that effector memory T cells populate healthy CNS parenchyma in humans and, independently, that CCR5-expressing lymphocytes as well as CCR5 ligands are enriched in the CNS of patients with multiple sclerosis. Apart from the recently described CD8+ CNS tissue-resident memory T cells, CRC researchers from Muenster identified a population of CD4+CCR5high effector memory cells as brain parenchyma-surveilling cells. In an interview with the German radio news channel NDR info they explain these latest insights. Listen to the radio report (in German):

Adapted from: Herich S, Schneider-Hohendorf T, Rohlmann A, Khaleghi Ghadiri M, Schulte-Mecklenbeck A, Zondler L, Janoschka C, Ostkamp P, Richter J, Breuer J, Dimitrov S, Rammensee HG, Grauer OM, Klotz L, Gross CC, Stummer W, Missler M, Zarbock A, Vestweber D, Wiendl H, Schwab N. Human CCR5high effector memory cells perform CNS parenchymal immune surveillance via GZMK-mediated transendothelial diapedesis. Brain.142(11):3411-3427.


Featured Publication: Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis

Mon, 27/01/2020

Münster. Cerebrospinal fluid (CSF) protects the central nervous system (CNS) and analyzing CSF aids the diagnosis of CNS diseases, but our understanding of CSF leukocytes remains superficial. Here, using single cell transcriptomics, SFB researchers identify a specific border-associated composition and transcriptome of CSF leukocytes. In an article published in Nature Communications, they show that multiple sclerosis (MS) – an autoimmune disease of the CNS – increases transcriptional diversity in blood, but increases cell type diversity in CSF including a higher abundance of cytotoxic phenotype T helper cells. A new analytical approach, named cell set enrichment analysis (CSEA) identifies a cluster-independent increase of follicular T helper (TFH) cells potentially driving the known expansion of B lineage cells in the CSF in MS. In mice, TFH cells accordingly promote B cell infiltration into the CNS and the severity of MS animal models. Immune mechanisms in MS are thus highly compartmentalized and indicate ongoing local T/B cell interaction.

Schafflick D, Xu CA, Hartlehnert M, Cole M, Schulte-Mecklenbeck A, Lautwein T, Wolbert J, Heming M, Meuth SG, Kuhlmann T, Gross CC, Wiendl H, Yosef N, Meyer Zu Horste G . 2020. Integrated single cell analysis of blood and cerebrospinal fluid leukocytes in multiple sclerosis. Nat Commun 11(1):247.


The key lies in cell metabolism: Neuroscientist and neurologist Luisa Klotz wins renowned Heinrich-Pette-Award

Tue, 22/10/2019

92. Congress of the German Society of Neurology in Stuttgart Foto: Claudius Pflug

Münster. For the third time the renowned neuroscience award “Heinrich Pette prize” goes to Münster, as this year Luisa Klotz was rewarded with the prestigious award for neuroscience researchers and clinicians at the congress of the German Society of Neurology in Stuttgart.

Neurologist and Neuroscientist Luisa Klotz received the award for her outstanding research in the field of Multiple Sclerosis and related neuroinflammatory disorders. She succeeds the director of the department of neurology Prof. Heinz Wiendl (2009) and the director of the institute of translational neurology Prof. Sven Meuth (2014). Read more . . .

 


Publication: Teriflunomide treatment for multiple sclerosis modulates T cell mitochondrial respiration with affinity-dependent effects.

Mon, 03/06/2019

Muenster. For the first time scientists from the University of Münster could show that multiple sclerosis (MS) alters the energy metabolism of T cells during acute phases of disease exacerbation. Therapeutic interventions targeting the metabolism of activated T cells display new potential avenues for treatment of patients with MS affecting around 250,000 people in Germany. The results of the study have recently been published in the renowned journal Science Translational Medicine. In a clinical trial, the authors investigated the effects of the MS drug teriflunomide in patients and analyzed its effects on immune cells. They could reveal that the drug specifically interferes with the energy metabolism of T cells and thereby preferentially affects highly active immune cells. “The drug specifically interferes with the activation of these cells already in the early initiation phase”, explains Luisa Klotz, first author of the article and principal investigator at the DFG-funded collaborative research centre 128 “Multiple Sclerosis”. Science Translational Medicine doi: 10.1126/ scitranslmed. aao5563.


Publication: Calcium influx through plasma-membrane nanoruptures drives axon degeneration in a model of multiple sclerosis.

Mon, 29/04/2019

Munich.  Here SFB researchers from Munich use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. Calcium can enter the axon through nanoscale ruptures of the axonal plasma membrane that are induced in inflammatory lesions. Neuron doi: 10.1016/ j.neuron.2018.12.023


Featured publication: Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk

Fri, 26/10/2018

In a large multi-cohort study, performed by the International Multiple Sclerosis Genetics Consortium (IMSGC) and published in Cell Magazine, unexplained heritability for multiple sclerosis (MS) is detected in low-frequency coding variants that are missed by genome-wide association study (GWAS) analyses, further underscoring the role of immune genes in MS pathology. The IMSGC was formed in 2003 with funding from the National Multiple Sclerosis Society and published results from the first GWAS in 2007 that identified the second and third susceptibility genes known to predispose people to developing MS. IMSGC later expanded to include more research groups from more countries, receiving grants to conduct larger GWAS studies. IMSGC brings together researchers from 15 different countries, among them scientists from the SFB-CRC 128 member organizations Technische Universität München and Universitätsmedizin Mainz. A pdf of the article may be found here (restricted access)


Munich Cluster for Systems Neurology (SyNergy) will be funded

Tue, 09/10/2018

Munich. The Cluster for Systems Neurology (SyNergy) by LMU and TUM will receive funding from 2019 on. Currently SFB PIs Prof. Reinhard Hohlfeld, Prof. Martin Kerschensteiner, Prof. Mikael Simons are also PIs of SyNergy projects.


Roland Liblau: “Immune targeting of CNS neurons” – Video available

Mon, 05/02/2018

Münster. On January 31, Prof. Roland  Liblau,  Director of the Pathophysiology Research Center at Toulouse Purpan, gave a lecture on “Immune targeting of CNS neurons: from mouse models to human diseases”. Prof. Liblau is one of the most visible neuroimmunologists worldwide which is why the SFB 128 is proud to make his lecture also available online. Just click here to see his presentation.


Elisabeth Schuh received SEED funding

Thu, 09/11/2017

Munich. SFB 128 researcher Elisabeth Schuh, MD, has been honoured by a young scientist’s studentship within the KKNMS SEED program. In her project „The role of the NLRP3 inflammasome in multiple sclerosis and experimental autoimmune encephalomyelitis“, Dr. Schuh analyses the influence of the NLRP3in MS. NLRP is a cytosolic protein complex in monocytes, macrophages and neutrophil granolucytes that regulated the production of inflammatory cytokines of the interleukin-1 family. In her project, Dr. Schuh wants to identify the population of myeloid cells involved in MS pathogenesis, with the aim of finding new pathways for therapeutic intervention that prevent autoimmune tissue damage.
The SEED program addresses scientists younger than 32 years who have not yet completed their medical training. The maximum funding is 32.000 € or 75 percent of the project’s budget. The remaining 25% have to be paid by the stipend’s employee.


Three new CRC associates

Tue, 17/10/2017

Muenster / Mainz / Munich. The CRC is proud to welcome three scientists as new associates: Muthuraman Muthuraman (Mainz), Anneli Peters (LMU) and Gerd Meyer zu Hörste (Münster).
All three are reputable neuroimmunologists, who add their in-depth knowledge of techniques and concepts to the existing team. Dr. Muthuraman Muthuraman is head of the scientific working group on biomedical statistics and multimodal signal processing at the Department of Neurology in Mainz (head: Prof. Frauke Zipp). Dr. Anneli Peters is project leader at the working group of Emeritus Director Prof. Hartmut Wekerle, focusing on the pathogenesis of multiple sclerosis. Dr. Gerd Meyer zu Hörste heads a scientific working group on understanding the interaction between nervous and immune system at the Department of Neurology in Muenster (head: Prof. Heinz Wiendl).


Genetically altered mice provide initial evidence that human gut bacteria can trigger multiple sclerosis

Tue, 12/09/2017

Munich. (LMU)  Multiple sclerosis (MS) is the most common inflammatory disease of the central nervous system. There are many indications that MS is an autoimmune disease in which immune cells “accidentally” attack the brain and spinal cord. However, as with other autoimmune diseases, the actual triggers of the autoimmune reaction are still unknown. A new study by scientists from the SFB 128 demonstrated for the first time that gut bacteria of MS patients are able to trigger an MS-like disease in an animal model. More . . .


Prof. Stefan Bittner receives Hertie Foundation medMS MyLab Research Funding

Mon, 11/09/2017

Mainz. Prof. Stefan Bittner joins fellow SFB 128 researcher Klaus Lehmann-Horn as the second 2017 recipient of research funding from the Hertie Foundation within the „MyLab” framework. Prof. Stefan Bittner will be funded by the program medMS My Lab to execute a new multi-year research project whose goal is to examine new mechanisms involved in neuronal degeneration in multiple sclerosis. More . . .


SFB researcher acquired Hertie foundation funding

Sun, 10/09/2017

Munich. SFB CRC 128 researcher Dr. Klaus Lehmann-Horn, Department of Neurology, has acquired 396.000€ of funding as part of the framework „MyLab“, which is sponsored by the Hertie foundation. The duration of the project „Antigen-driven affinity maturation of B lymphocytes in meningeal ectopic lymphoid tissue in a model of Multiple Sclerosis“ will be 5 years, starting on January 1st.


Visualizing context-dependent calcium signaling in encephalitogenic T cells in vivo by two-photon microscopy

Sat, 01/07/2017

Munich. In a recently published PNAS paper we visualized intracellular calcium in the encephalitogenic T cells in vivo by using FRET based sensor. The T cells showed short and long lasting calcium signaling dependent on their interaction partners. The blocking of the calcium signaling can be used as target of therapeutic treatments . More . . .


SFB researcher wrote paper of the month

Thu, 04/05/2017

Muenster. The article “Rapid and efficient generation of oligodendrocytes from human induced pluripotent stem cells using transcription factors” by SFB researcher Marc Ehrlich has been named “paper o the month” of May by the Medical Faculty Muenster. With this award the faculty honors excellent examples for the continuous output of its about 2.000 scientisits.


SFB Scientists reprogram skin cells to brain cells to facilitate neurological research

Thu, 16/03/2017

SFB scientists Prof. Tanja Kuhlmann und Dr. Marc Ehrlich generate oligodendrocytes from skin cells (photo: FZ/E. Deiters-Keul)

Münster. (mfm/jr) Whether it be math, writing, reading or learning a new language: brain cells give us astonishing brainpower every day. When these cells are damaged by neurological diseases, cells cannot be simply sampled and analyzed in a petri dish. Scientists from the University of Münster and the Max Planck Institute for Molecular Biomedicine developed a new protocol to generate their brain cells of interest, oligodendrocytes, from skin. The team in Münster belongs to the few labs worldwide that have established this technique successfully in their lab; however the team in Münster can do this now much faster and more efficiently – with significant benefit for research. More .  . .

 


Featured publication: Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier

Wed, 23/11/2016

Münster – The enzymes gelatinase A/matrix metalloproteinase-2 (MMP-2) and gelatinase B/MMP-9 are essential for induction of neuroinflammatory symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). In the absence of these enzymes, the disease does not develop. SFB128 scientists of Prof. Dr. Lydia Sorokin’s group, therefore, investigated the cellular sources and relative contributions of MMP-2 and MMP-9 to disease at early stages of EAE induction. They demonstrated that MMP-9 from an immune cell source is required in EAE for initial infiltration of leukocytes into the central nervous system and that MMP-9 activity is a reliable marker of leukocyte penetration of the blood-brain barrier.
The neuroscientists then developed a molecular imaging method to visualize MMP activity in the brain using fluorescent- and radioactive-labeled MMP inhibitors (MMPis).
By using radioactive MMP ligand in EAE animals the Muenster neuroscientists produced positron emission tomography (PET) images of MMP activity in patients with MS.
In contrast to traditional T1-gadolinium contrast-enhanced MRI, MMPi-PET enabled tracking of MMP activity as a unique feature of early lesions and ongoing leukocyte infiltration.
MMPi-PET therefore allows monitoring of the early steps of MS development and provides sensitive, noninvasive means of following lesion formation and resolution in murine EAE and human MS, the neuroscientists conclude. Their work was part of the SFB projects B03 and Z02.


Research into “accident black spots“: new hypothesis on the origins of centres of inflammation in multiple sclerosis

Mon, 21/11/2016

Münster (mfm/sk-sm) – The scenario resembles a serious motor accident: a car has spun out of control, breaches the central crash barrier and collides with the oncoming traffic. In the case of multiple sclerosis, harmful T-cells break through the protective blood-brain barrier and thus penetrate into the central nervous system (CNS), where they trigger a destructive inflammation. What’s special about this is that evidently the CNS also has “accident black spots” – in other words, places where an especially high number of centres of inflammation are be found. Neuro-immunologists at Münster University have now found out why this is so. More . . .

PD Dr. Luisa Klotz and Ivan Kuzmanov at work in the laboratory (Photo: FZ/UKM)

PD Dr. Luisa Klotz and Ivan Kuzmanov at work in the laboratory (Photo: FZ/UKM)


Milestone in MS research: neuroimmunologists find cause of deficit in body’s own immune system

Tue, 25/10/2016

Within a project of the SFB 128, scientists from the universities in Münster and Munich have discovered what precisely goes wrong in the body in the case of multiple sclerosis (MS). At the same time the neuroscientists were able to demonstrate that for MS, which occurs in bouts, there is a therapy which is tailor-made to eliminate the deficit. More Information . . .


Stipend for International Cooperation with Turkey (Project B08)

Fri, 04/03/2016

Dr. Atay Vural has been awarded a stipend by the Alexander von Humboldt Foundation to spend time in the group of Prof. Edgar Meinl to conduct research into MOG-Ak, which is part of the work done in the CRC-TR128 B08 project. After Dr. Vural’s stay in Prof. Meinl’s group, he will return to his home country of Turkey, where he will employ the techniques learnt in Germany in further research projects.


Two young researchers from CRC TR128 awarded Helmut Bauer Prize 2015

Fri, 04/03/2016

Sarah Laurent und Franziska Thaler, scientists working on the B08 project of the CRC TR128, have been awarded the Helmut Bauer Prize 2015 for young researchers for their work on the survival, regulation and activation of B cells in multiple sclerosis (see publications below). More information on this prize can be found in this press release (in German).

Laurent et al. γ-Secretase directly sheds the survival receptor BCMA from plasma cells Nat Commun 2015 6:7333

Hoffmann et al. The immunoregulator soluble TACI is released by ADAM10 and reflects B cell activation in autoimmunity J Immunol 2015 194(2):542-52

 


Heinz Wiendl awarded Sobek Prize for MS research

Wed, 27/01/2016

Prof. Heinz Wiendl, Co-Speaker of the CRC-TR-128, has been awarded the prestigious Sobek Research Prize 2015 for his contributions to research into multiple sclerosis. More information can be found in this press release (in German)


CRC Principal Investigator, Prof. Jacqueline Trotter, together with Prof. Thomas Mittmann, discuss the role of glial cells in neuronal signalling on Deutschland Funk radio

Thu, 04/06/2015

You can read the associated article and listen to the interview on the Deutschland Funk website or using the player below.


Nina Wettschureck awarded prize for mechanistic elucidation of MS therapy

Tue, 21/04/2015

Nina Wettschureck (MPI Bad Nauheim) from the CRC-TR-128, together with Markus Schwaninger (University of Lübeck), has been awarded the Novartis prize for therapy-relevant pharmacological research. The prize, which carries a value of €10,000, was presented at the Annual Conference of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) on 12 March 2015 in Kiel.

More details can be found in this press release, and the research for which the prize was awarded was reported in the following publication in The Journal of Clinical Investigation:

Chen H, Assmann JC, Krenz A, Rahman M, Grimm M, Karsten CM, Köhl J, Offermanns S, Wettschureck N, Schwaninger M: Hydroxycarboxylic acid receptor 2 mediates dimethyl fumarate’s protective effect in EAE. The Journal of Clinical Investigation. doi:10.1172/JCI72151 


CRC scientists Nicholas Schwab and Johanna Breuer win Helmut-Bauer Young-Scientist Prize for MS research

Mon, 02/02/2015

Congratulations to the CRC Scientists Nicholas Schwab and Johanna Breuer from the Neurological Clinic of the University Hospital Münster who were awarded the Helmut-Bauer Young-Scientist Prize for MS Research. (more…)


CRC scientists discover new protection mechanism for nerve cells after they are damaged

Thu, 22/01/2015

CRC scientists from the University Medical Center Mainz, together with colleagues from the University of Virginia, have identified a new mechanism that mediates repair of nerve cells after damage to the central nervous system. (more…)


International Neuroimmunology Conference in Mainz

Fri, 05/12/2014

From 9-13 November 2014, over 1000 neuroimmunologists from all over the world met at the 12th International Congress for Neuroimmunology in Mainz. (more…)


CRC Young Researchers win prizes at prestigious conferences

Fri, 26/09/2014

Congratulations to Dr. Nicholas Schwab and Dr. Tilman Schneider-Hohendorf, both from the Department of Neurology, University of Münster, who received prizes at two prestigious conferences recently! (more…)


How adhesion molecules help pathogenic T cells to find their way over the blood-brain-barrier

Tue, 16/09/2014

Münster scientists: Even a highly efficacious MS drug cannot stop certain inflammatory cells (more…)


CRC Scientist Krishnaraj Rajalingam becomes Heisenberg Professor for Cell Biology in Mainz

Mon, 21/07/2014

Congratulations to Krishnaraj Rajalingam (Project B9) who has received a prestigious Heisenberg Professorship for cell biology at the Institute for Immunology of the University Medical Center of the Johannes Gutenberg University Mainz. This is the first such professorship for the JG University of Mainz. Further details can be found here.


CRC Retreat in Munich

Fri, 23/05/2014

Thanks to all those who attended the CRC Retreat in Munich in May. As well as having great weather, there were also excellent scientific talks and lively discussion during the poster session and in the Biergarten afterwards.

Special thanks go to the organizer Jutta Marks, who did a fantastic job in making this such an enjoyable meeting for all concerned.

Retreat Munich 2014


Münster: Scientists demonstrate the influence of sunlight exposure on the incidence of autoimmune diseases

Thu, 15/05/2014

(more…)


Skills Workshop in Frankfurt

Fri, 20/12/2013

Thank you to all those who attended the skills workshop “Career Options in Academia and Beyond” on 18.12.2013 in Frankfurt. (more…)


CRC Retreat in Münster

Thu, 12/12/2013

Thank you to all who attended the CRC Retreat in Münster on 28-29.11.2013. It provided a great opportunity for CRC members to meet and be updated on the progress of all research projects with lively poster sessions, interesting talks and stimulating discussion. (more…)


Videoconference of Prof. Gold’s talk

Thu, 12/12/2013

Thanks to all who participated in the videoconference of Prof. Gold’s talk in Mainz on 10.12.2013. (more…)


Successful videoconference of Prof. Wekerle’s talk

Fri, 22/11/2013

 

On Thursday 21.11.2013, we successfully used our new videoconferencing equipment here in Mainz to watch Prof. Hartmut Wekerle give a very interesting talk in München. Thanks to all those who helped to make this technically possible. (more…)


Nature Medicine paper from Münster research groups

Fri, 16/08/2013

Bittner et al’s paper entitled Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS published in Nature Medicine is now available to be viewed here.


Neurosymposium

Thu, 08/11/2012

08.11.2012, 13:30: Neurosymposium:The Cell Biology of CNS Development, Myelination and Multiple Sclerosi, @ Johannes Joachim Becherweg 13, HS19, Mainz