Objective
Brain microglia are characterized as uncommitted myeloid progenitors of immature dendritic cells (DC) or macrophages. Recently, it has been demonstrated that resident microglia can be skewed by astrocyte or microglia-produced cytokines to differentiate into immature DC.
Thereafter, various additional stimuli can induce differentiation into mature DC that have the potential to present (self) antigen and to prime naïve (autoreactive) T cells. We believe that these microglia-derived, mature DC play a crucial role in the pathogenesis of multiple sclerosis by inducing, shaping and/or sustaining autoimmune responses. However, they will do so only after having received the signals to mature in the brain itself. Key molecules in this process are the C-type lectin receptors (CLR) and Toll-like receptors (TLR). In addition, it is becoming increasingly clear that the combination of signals received via CLR and/or TLR is a decisive factor in determining what type of T cell response a DC will induce. We propose to identify which CLR and/or TLR are important for the maturation of microglia into DC and for the subsequent induction of an autoimmune response:
-Which CLR/TLR are expressed by different subsets of glia cells in vitro and in situ?
-Which (endogenous) factors influence the maturation of microglia into (im)mature DC and what are the roles of CLR/TLR in this process?
-How do different (infectious and non-infectious) insults lead to the induction of functionally distinct subsets of autoreactive T cells and what are the roles of different TLR in this process?
In vitro approaches, brought in by the fellow, form the heart of the project and will be incorporated in the extensive in vivo expertise present in the institute. The integrative approach will hopefully lead to new insights in how the brain plays a role in shaping the immune response against itself, allowing modulation in favour of inducing tolerance rather than the induction of an autoimmune response.
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.
- natural sciences biological sciences zoology mammalogy primatology
- natural sciences biological sciences neurobiology
- medical and health sciences basic medicine neurology multiple sclerosis
- medical and health sciences basic medicine immunology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-11
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Funding Scheme
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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.
Coordinator
RIJSWIJK ZH
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.