Summary
Regulatory T cells (Tregs) are formed through the expression of the transcription factor Foxp3 in T cells, resulting in the rewiring of the cell function into an immunosuppressive phenotype. Recently, it has been proposed that Tregs also have additional tissue-specific physiological roles when resident in different tissues. For example, tissue-specific Tregs residing in the muscle and adipose tissue possess immunological and non-immunological functions in these tissues, distinct from the generic Tregs in circulation. Currently, research into tissue-specific functions of Tregs, or any other migratory cell type, is limited by the available research tools. A vital part of immunological studies is cell depletion, yet a major limitation of all available methods is that they deplete target cells across the entire organism. This makes it extremely difficult to ascertain the function of tissue-resident Tregs, as systemic deletion results in severe autoimmunity, confounding the study of tissue-specific subsets. In order to assess these tissue-resident subsets new research tools are required to deplete the target cells in a specific anatomical region while leaving the same cell type unaffected in other organs. This project proposes to generate new synthetic biology tools for depleting tissue-resident cells and then to apply these tools to the study of tissue-resident Tregs in the brain, lung, liver, kidney and pancreas, thus creating a comprehensive atlas of tissue-specific functions. These studies will be extended by systematic molecular, cellular and kinetic analysis using existing innovative methods established in the laboratory. Finally, our tissue-specific deletion system will have a profound impact on immunology beyond the direct scope of the project, as the tools will be developed to allow flexible application to any cell type. In essence, this is a field of research currently held back by the absence of appropriate tools, waiting for the generation of a new toolkit.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/681373 |
| Start date: | 01-06-2016 |
| End date: | 30-11-2021 |
| Total budget - Public funding: | 1 999 535,00 Euro - 1 999 535,00 Euro |
Cordis data
Original description
Regulatory T cells (Tregs) are formed through the expression of the transcription factor Foxp3 in T cells, resulting in the rewiring of the cell function into an immunosuppressive phenotype. Recently, it has been proposed that Tregs also have additional tissue-specific physiological roles when resident in different tissues. For example, tissue-specific Tregs residing in the muscle and adipose tissue possess immunological and non-immunological functions in these tissues, distinct from the generic Tregs in circulation. Currently, research into tissue-specific functions of Tregs, or any other migratory cell type, is limited by the available research tools. A vital part of immunological studies is cell depletion, yet a major limitation of all available methods is that they deplete target cells across the entire organism. This makes it extremely difficult to ascertain the function of tissue-resident Tregs, as systemic deletion results in severe autoimmunity, confounding the study of tissue-specific subsets. In order to assess these tissue-resident subsets new research tools are required to deplete the target cells in a specific anatomical region while leaving the same cell type unaffected in other organs. This project proposes to generate new synthetic biology tools for depleting tissue-resident cells and then to apply these tools to the study of tissue-resident Tregs in the brain, lung, liver, kidney and pancreas, thus creating a comprehensive atlas of tissue-specific functions. These studies will be extended by systematic molecular, cellular and kinetic analysis using existing innovative methods established in the laboratory. Finally, our tissue-specific deletion system will have a profound impact on immunology beyond the direct scope of the project, as the tools will be developed to allow flexible application to any cell type. In essence, this is a field of research currently held back by the absence of appropriate tools, waiting for the generation of a new toolkit.Status
CLOSEDCall topic
ERC-CoG-2015Update Date
27-04-2024
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