Objective
Dendritic cells (DCs) are key regulators of both immunity and tolerance by controlling activation and polarization of effector T helper cells (Th) and regulatory T cell responses (Treg). Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to changes in cellular metabolism. However, only recently, based on studies with T cells and macrophages, the picture is emerging that manipulation of cellular metabolism can be used to shape immune responses. This field of immunometabolism is rapidly evolving as one of the new frontiers in science. Nonetheless, little is known about the metabolic processes that support DC activation or about the metabolic requirements for DCs to drive Th1, Th2 or Treg responses. My proposal aims to fill this gap and focuses on the novel concept that cellular metabolism regulates the immune-polarizing properties of DCs.
Based on my recently published work and preliminary data, I hypothesize (1) that DCs priming Th1 responses are metabolically characterized by a switch to glycolytic metabolism, whereas Th2- or Treg-polarizing DCs, have a catabolic kind of metabolism that is dependent on mitochondrial fatty acid oxidation and oxidative phosphorylation and (2) that these states of metabolism are required for their immune-polarizing capacity.
To address this, my project aims (a) to characterize and compare the metabolic profiles of Th1-, Th2- and Treg-polarizing DCs and (b) to determine whether their metabolic programs underpin their T cell-polarizing capacity. (c) Based on these findings I aim to determine whether deliberate modulation of glycolytic or mitochondrial metabolism can alter the immune-polarizing capacity of DCs in such a way that they become either more immunogenic or tolerogenic in vivo. These studies can readily contribute to the development of novel metabolism-based strategies for improving DC-based immunotherapy.
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 chemical sciences electrochemistry electrolysis
- natural sciences biological sciences biochemistry biomolecules lipids
- medical and health sciences basic medicine immunology immunotherapy
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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.
FP7-PEOPLE-2013-CIG
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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.
MC-CIG - Support for training and career development of researcher (CIG)
Coordinator
2333 ZA Leiden
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.