PROJECT: JTC2014: MELTRA-BBB

MEchanisms of Lymphocytes TRansmigration Across the Blood Brain Barrier

Abstract

Activated T cells can enter the CNS also when there are no obvious signs of inflammation. These cells enter the CNS in order to survey this organ for bacterial or viral infection, and possibly to eliminate malignant cells. But once the CNS is the focus of an attack, such that is seen in multiple sclerosis patients, its gates are opened so that a dramatic inflammatory process occurs. The mission of MELTRA-BBB is to investigate the early steps of CNS infiltration, and understand what allows B and T cells to pass the BBB and initiate the inflammatory process. Our consortium is composed of members that have all been working for many years in the field of multiple sclerosis and its mouse model experimental autoimmune encephalomyelitis. Together, we have a rare combination of expertise in mouse genetics, the biology of endothelial cells, immunology, neuropathology and intravital imaging that makes it an ideal team to investigate mechanism of the requirements of lymphocyte entry to the CNS. We will use genetic methods to delete cytokine receptors or to ablate specific cells of the immune system, and follow the development of disease in these mice. We will use cell culture systems to translate the mouse findings to the human system. We expect that by the combination of studies in experimental models and human disease our results will have broad relevance for inflammatory diseases of the CNS as a whole and will be utilized to design better therapies for the patients of these diseases.

Keywords

Gene targeting in the brain, Molecular modelling techniques, Blood Brain Barrier, (epi)genetic approaches, Multiple sclerosis, Cytokine receptors, T cells, B cells

Call topic

Neuroinflammation

Proposed runtime

2014 - 2018

Project team

Ari (Coordinator)
Germany (BMBF)
Prat
Canada (CIHR)
Lassmann
Austria (FWF)
Flügel
Germany (BMBF)
Liblau
France (ANR)
Penesova
Slovakia (SAS)