Objective
The adaptive immune system protects us from nocuous microbes, yet excessive immune reactions can lead to the development of autoimmunity. The initiation of adaptive immune responses takes place in lymphoid organs, including peripheral lymph nodes (PLN). Inside PLN, T cells become activated through the molecular interactions of the T cell receptor with cognate peptide-MHC (pMHC) molecules and costimulatory molecules on dendritic cells (DC). TCR-mediated signals lead to the activation of the phosphoinositol-3-kinase (PI3K) pathway via the PI3Kδ isoform, which is required for full T cell activation in vitro.
However, little is known about the role of the PI3Kδ during primary and secondary in vivo T cell activation. Here, we will use twophoton microscopy (2PM) to observe the interactions of antigen-specific control and PI3Kδ-mutant CD4+ T cells and pMHC-loaded DC deep inside PLN of live, anesthetized mice. Comparing the dynamic interaction parameters obtained in 2PM imaging with the flow cytometric analysis of the activation status of control and PI3Kδ-mutant T cells, we will delineate the precise contribution of the PI3Kδ for primary T cell activation in vivo.
We will furthermore perform an analysis of the secondary activation of control and PI3Kδ-mutant effector CD4+ T cells in a mouse model of antigen-induced arthritis. Therefore, we will establish an intravital knee-joint 2PM model to follow the dynamic behavior of control and PI3Kδ-mutant effector T cells with antigen-presenting macrophages in the inflamed tissue. We will combine imaging data with disease scoring, flow cytometry and the use of a PI3Kδ-specific pharmacological inhibitor for a comprehensive analysis of PI3Kδ function at sites of inflammation.
In summary, we propose to perform an in-depth analysis of the role of PI3Kδ during adaptive immune response initiation and maintenance. This is also clinically relevant since PI3Kδ inhibitors are in development for immunomodulation.
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 clinical medicine rheumatology
- natural sciences physical sciences optics microscopy
- medical and health sciences basic medicine immunology
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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-2010-IIF
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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.
Coordinator
3012 BERN
Switzerland
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.