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

Wed, 19/01/2022
One drug – different effects: Metabolism of immune cells influences mode of action and could be an indicator for side effects
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 […]...more
Tue, 14/12/2021
Save the date: 2nd Inflammation & Imaging Symposium
Münster. Save the date: 12-14 September 2022! We cordially invite you to join this international symposium, jointly organized by the research networks CRC 1450, CRC 1009, CRC 1348, CRU 342, CRC/TR 128 and the Cells in Motion Interfaculty Centre at the University of Münster. At the same time, we will officially open the new research […]...more
Mon, 09/08/2021
Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity
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 […]...more