Molecular mechanisms and sites of action of the gelatinases in autoimmune CNS inflamma-tion: do MMP-2/-9 contribute to meningeal inflammation and secondary cortical damage?

B03

Meningeal inflammation results in cortical damage and correlates with disability in MS, but is poorly understood. We showed that gelatinases (matrix metalloproteinase (MMP)-2 and -9) control leuko-cyte penetration of the blood-brain barrier at postcapillary venules and propose that they serve simi-lar functions at the meningeal-brain border. We will investigate gelatinases in the meninges of MS patients and mouse experimental atoimmune encephalomyelitis (EAE), identify novel gelatinase substrates that induce meningeal inflammation, and test these substrates in patients. Meningeal T cells will be tracked in mice lacking MMP-2/-9. By understanding meningeal inflammation, we aim to understand drivers of disability in MS. Our project is guided by these questions:

    1. What is the difference between the meninges of MS patients and healthy controls? This question will be answered based on an unbiased cellular map of the meninges in human MS which will be compared with cortical pathology.
    2. Whereare gelatinases expressed? H how do they contribute to inflammation in the meninges?
    3. Which gelatinase substrates mediate meningeal inflammation induced by Th17 cells? Can they be traced in cerebrospinal fluid?
    4. Do gelatinases affect meningeal T cell trafficking in vivo?

B03

MMP-2/-9 actvity at sites of leukocyte penetration of the CNS parenchyma
in postcapillary venules and meninges

 

Principal Investigators:
Univ.-Prof. Dr. rer. nat. Lydia Sorokin
Institut für Physiologische Chemie und Pathobiochemie
Münster
sorokin@uni-muenster.de

Priv.-Doz. Dr. med. Gerd Meyer zu Hörste
Klinik für Neurologie mit Institut für Translationale Neurologie
Münster
gerd.meyerzuhoerste@ukmuenster.de

News

Thu, 28/01/2021
BioNTech Publishes Data on Novel mRNA Vaccine Approach to Treat Autoimmune Diseases in Science
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 […]...more
Wed, 20/01/2021
A new study on neurological manifestations of severe COVID-19 reveals nervous system immune deficiency
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 […]...more
Fri, 15/01/2021
Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity
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 […]...more