Objective
Our understanding of T cell differentiation impacts on vaccine development and on the treatment of (auto) immune disorders. T cells are key players in inflammation, a crucial component of the immune response to pathogens that causes severe damage to the host when uncontrolled. The cytokines Interferon-(IFN-) and Interleukin-17 (IL-17) are critical mediators of the proinflammatory activity of T cells usually designated as “T helper 1” (Th1) and Th17, respectively.
Here we propose to investigate the contribution of all T cell lineages - CD4+ and CD8+ cells, and NKT cells – to global Th1 or Th17 immune responses, using various tools including a IFN-/IL-17 double reporter mouse. Importantly, we will study Th1/ Th17 differentiation in vivo, inmodels of infection with Plasmodium berghei or Mycobacterium tuberculosis. We will analyse theindividual and combined contributions of the distinct T cell subsets, their cellular interactions andpotential interdependence in lymphoid organs and in target organs of infection.
We further envisage a molecular understanding of how innate (and NKT) and adaptive (CD4+ and CD8+) T cell subsets acquire their respective capacities to produce IFN-or IL-17 in vivo. We will dissect (pre-/ post-) transcriptional mechanisms of regulation of Ifng and Il17 expression in the various T cell subsets, ultimately at the single-cell level. We aim at characterizing networks of transcription factors and microRNAs that regulate Th1/ Th17 differentiation either in all or in specific T cell subsets. We are particularly interested in addressing the constitutive expression of IFN-or IL-17 by innate T lymphocytes, which is set up in the thymus. We will define the molecular components of this “developmental pre-programming” of and NKT cells in comparison with the mechanisms of peripheral induction of CD4+ Th1/ Th17 cell differentiation upon infection.
By contrast to the generalized focus on CD4+ T cells, this project will consider Th1/ Th17 differentiation of all T cell lineages and their in vivo contributions to relevant models of infection. I believe this holistic view of organism-based immune parameters and their underlying molecular mechanisms, down to the single-cell level, will significantly advance our understanding of how the Immune System works.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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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.
Topic(s)
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.
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2010-StG_20091118
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Funding Scheme
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.
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.
Host institution
1649 028 Lisboa
Portugal
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.