Project description
Tissue cytokines are at the centre of immune cell-driven inflammation in myocarditis
Myocarditis is an acute inflammatory heart disease caused by the body’s immune system in response to an infection or other triggers. Recent studies identified cross-reactive CD4+ T cells as central players in the inflammatory cardiomyopathy pathogenesis, in which activation is controlled by the tissue cytokines of the transforming growth factor-beta superfamily. The goal of the EU-funded CardiacStroma project is to decipher the molecular pathways that control the interaction of immune cells with stromal cells in the cardiac tissue during inflammation reaction. The project will identify novel targets for the treatment of myocarditis and inflammatory cardiomyopathy, validate antibodies that ameliorate cardiac inflammation, and provide a comprehensive analysis of the cellular and molecular changes during cardiac inflammation.
Objective
Myocarditis is an acute inflammatory heart disease that can progress to chronic cardiomyopathy and heart failure. Since there is no specific treatment recommendation available for myocarditis and subsequent inflammatory cardiomyopathy, there is an urgent need to dissect the pathological principles underlying cardiac inflammation and to target those molecular pathways that are at the core of the pathological process.
My recent research places cross-reactive CD4+ T cells at the center of inflammatory cardiomyopathy pathogenesis. The activation and sustenance of cardiotropic T cells is controlled in immune cell-nurturing niches that are generated by fibroblastic stromal cells through the provision of tissue cytokines of the TGF-beta superfamily. The overarching goal of this project is therefore to decipher the molecular pathways that govern the interaction of immune cells with stromal cells in the cardiac tissue through the combination of state-of-the-art pre-clinical models, novel methods from quantitative systems biology, functional validation by antibody blockade, and assessment of the translational relevance through the analysis of cardiac biopsies from human patients. The generation of antibodies that neutralize a distinct set of tissue cytokines or their inhibitors will not only serve as functional validation, but will open possibilities for future translational development. Moreover, the utilization of spatial transcriptomics for the analysis of human heart samples will open new avenues for innovative research both in immunology and in cardiology.
Overall, I expect that the planned research program will deliver (i) novel targets for the treatment of myocarditis and inflammatory cardiomyopathy, (ii) validated prototype antibodies that ameliorate cardiac inflammation through the manipulation of stromal cell-immune cell interaction, and (iii) a comprehensive analysis of the changes in the cellular and molecular landscape during cardiac inflammation in humans.
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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciencesbasic medicineimmunology
- medical and health sciencesclinical medicinecardiology
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Funding Scheme
ERC-ADG - Advanced GrantHost institution
9007 St. Gallen
Switzerland