Objective
Asthma is a chronic inflammatory airway disease in which the transcription factor NF-kB plays a crucial role. NF-kB controls the activation of mast cells and dendritic cells (DC) that contribute to disease pathogenesis. Activation of NF-kB is tightly regulated by ubiquitination and deubiquitination of signaling intermediates. Studies in the host laboratory identified several deubiquitinating enzymes like A20 (also known as TNFaip3) and its binding partners to set the tone for NF-kB activation. A20 deficient mice succumb from an autoimmune inflammatory disease, through exaggerated responses induced by Toll like receptor (TLR) triggering, precluding a detailed analysis of the function of A20 in vivo. In the current proposal we will study the effect of cell-specific deletion of A20 on allergic airway inflammation, employing recently generated conditional A20 deficient animals, and crossing them with DC-specific and mast cell-specific deletor mice. In mast cells and DCs, we will study various ubiquitination and deubiquitination signaling events in the NF-kB pathway following activation with TLR agonists, cytokines and house dust mite allergen (HDM). Subsequently, the effects of cell-specific deletion of A20 on cellular function will be ascertained in vitro, using the most recent techniques in cell biology and cellular immunology. Next, we will study the effects of cell-specific deletion of A20 on the function of mast cells and DCs in vivo, focusing specifically on mast cell degranulation, passive cutaneous anaphylaxis, DC activation and parameters of T cell activation and differentiation. Finally, mast-cell or DC-specific A20 deficient mice will be subjected to asthma protocols driven by ovalbumin and HDM and salient features of asthma like eosinophilia, Th2 cytokine production and bronchial hyperreactivity will be studied. Upon completion of this project we will have a clear understanding of the regulatory role of A20 in the immune system and allergic disease.
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 pneumology asthma
- natural sciences biological sciences cell biology
- medical and health sciences basic medicine immunology
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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.
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-IEF-2008
See other projects for this call
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
9052 ZWIJNAARDE - GENT
Belgium
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.