Project characteristics
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Project aims
Macrophages (MFs) and myeloid dendritic cells (mDCs) play a crucial role in immune and inflammatory responses. Besides being cells that capture and destroy pathogens and present antigens to T cells, MFs and mDCs are now well described as a heterogeneous group of cells with various specialized activities in different anatomical locations. Many of these activities appear to be antagonistic in nature, e.g. pro-inflammatory versus anti-inflammatory, immunogenic versus tolerogenic, and tissue-destructive versus tissue repair activities. The different functional properties of these subsets of cells are characterized by the production of a distinct set of mediators and expression patterns of various receptors, offering a whole range of diagnostic and therapeutic perspectives.
Partners in the consortium of the current SBO project have developed tools to analyze the genetic signatures of myeloid cells (MCs) and have generated a knowledge platform with information about molecular markers expressed by MCs in vivo in different activation states and in different inflammatory mouse models. In the current project we want to use this knowledge platform to validate selected MC (MF and mDC) markers for the purpose of in vivo targeting of inflammatory MCs.
More specifically, the aims are:
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as a first priority, we aim to evaluate the feasibility of tracking inflammatory processes, their evolution (spontaneous and in response to drug treatment) and the underlying mechanisms in living organisms through visualization of (anti-) inflammatory myeloid cells (and the MC markers they express) using in vivo imaging technology. Hereby, myeloid cell markers will be evaluated as targets for radioactive tracers or reporter genes;
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as a second priority, MC markers will be validated as targets for modulating inflammatory MC function in order to scrutinize the functional implication of the selected MC markers in the inflammatory process, thereby providing information on the molecular basis of the inflammatory process and leading potentially to therapeutic applications.
Proofs of principle will be generated in experimental models for pulmonary inflammation - Pseudomonas pneumonia, hypersensitivity pneumonitis (HP) and asthma - and rheumatoid arthritis (RA). These highly prevalent diseases present with chronic inflammation, which imposes a heavy burden on the patient and are likely to benefit from monitoring and/or selective attenuation of MC activity. Partners providing expertise in these various animal models of inflammation have been recruited for the consortium.
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Project partners
Coordinator: Patrick De Baetselier
Laboratory of Cellular and Molecular Immunology
Vrije Universiteit Brussel
VIB Department Molecular and Cellular Interactions
Rudi Beyaert
Molecular Signal Transduction in Inflammation Unit
Universiteit Gent
VIB Department for Molecular Biomedical Research
Axel Bossuyt
In Vivo Cellular and Molecular Imaging Center
Vrije Universiteit Brussel
Universitair Ziekenhuis Brussel (UZ Brussel)
Johan Grooten
Molecular Immunology Unit
Department of Molecular Biology
Universiteit Gent
Patrick Matthys
Laboratory of Immunobiology
Rega Institute for Medical Research
Katholieke Universiteit Leuven
Kristiaan Thielemans
Laboratory of Molecular and Cellular Therapy
Vrije Universiteit Brussel
Universitair Ziekenhuis Brussel (UZ Brussel)
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