Project description
Profiling immune cell traffic across the blood-CSF barrier
The brain is protected from potentially harmful blood constituents in part by the blood-cerebrospinal fluid (CSF) barrier. Scientists recently discovered that this physical barrier does not prevent large immune cells from crossing as previously believed. Given that harmful immune cell trafficking is implicated in brain autoimmunity such as neuropsychiatric lupus (neuro-lupus), enhanced trafficking might be a pathway to tumour treatment or even treatments for neurodegenerative diseases. The ERC-funded CNS Hidden Door project will investigate this by leveraging their discovery of enhanced leukocyte migration through rather than between cells of the brain-CSF barrier in neuro-lupus. Using high-tech methods, they will classify cell types involved, identify trafficking pathways and develop approaches to regulate the process.
Objective
Immune cells continuously traverse our body, crossing vascular and epithelial barriers; from lymphatic organs into the blood, and from the blood into various tissues for surveillance or to fight infection. However, the brain has long been considered an immune-privileged organ. Barriers protecting the brain against infection or harmful toxic agents were also thought to block entry of immune cells, leaving immune functions to brain-resident microglia cells. This dogma was recently overturned when it became clear that immune cells cross, mainly for surveillance, especially at the Blood-CSF barrier. Furthermore, while harmful immune cell trafficking is a hallmark of brain autoimmunity, e.g. Multiple Sclerosis and Neuro-Lupus, enhanced trafficking might help to fight brain tumours, and even to resolve neurodegenerative conditions, e.g. Alzheimer’s Disease. Yet the study of immune cell trafficking across the Blood-CSF barrier is severely hampered by a shortage of suitable methodologies.
We investigated Blood-CSF barrier dysfunction in Lupus and discovered a brain lymphoid structure with enhanced immune cell trafficking. Dominant transepithelial leukocyte migration (through, rather than in between, cells) will enable us to catch the trafficking events ‘red-handed’ and to identify molecular and cellular trafficking mechanisms. Harnessing innovative methodologies involving single-cell RNAseq, Super-Resolution microscopy, Imaging cytometry, and genetic/pharmacological interventions, we aim to decipher the fundamental question of how leukocytes enter the brain. We will classify specialized immune and epithelial barrier cell types, identify trafficking molecular pathways, and develop approaches to regulate the process. We will also assess this barrier involvement in the pathobiology of human Neuro-Lupus disease.
Understanding immune trafficking mechanisms may be the key to a specialized brain portal, leading to therapeutics that can modulate brain-immune interactions.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences basic medicine neurology dementia alzheimer
- natural sciences physical sciences optics microscopy super resolution microscopy
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine hematology
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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(opens in new window) ERC-2022-COG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
91904 JERUSALEM
Israel
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