Project description
Scientist sleuths track activated T cells and their informants in vivo
Dendritic cells (DCs) of the immune system initiate the adaptive immune response and play an important role in inflammation and its homeostasis. Much like a policeman presenting a suspect's clothing to a police dog, DCs capture and process pathogens and present identifiers (antigens) to the T cells to unleash the T-cell response. Discovered nearly half a century ago, T cells are now known to be a heterogeneous group of cells in both structure and function. However, the significance of these differences remains to be seen. The EU-funded SYNVIVO project, with its established technique to label interactions between immune cells in vivo, is tracking activated T cells to determine the relationship between their fate and the DCs that activated them.
Objective
CD4+ T cells are crucial component of our immune system: they support distinct types of proinflammatory responses key for pathogen clearance, maintain tolerance and suppress harmful inflammation. To perform this multitude of functions, naïve CD4+ T cells first undergo activation through direct contact with dendritic cells (DCs), a highly heterogeneous compartment including several populations of migratory and resident cells. These interactions lead to selection of antigen specific T cell clones, followed by their proliferation and differentiation into distinct subsets showing specialized effector programs or polarizations. Despite the essential role of dendritic cells in the activation and polarization of naïve CD4+ T cells, we have limited information available on both the identity of DC involved in priming and the molecular messages exchanged upon DC-CD4+ T cell interaction in different types of response. Recently, I developed an innovative technology that allows us for the first time to label interactions between immune cells in vivo. This method, which we called LIPSTIC, relies on the labeling of genetically engineered receptor–ligand pairs mediated by the enzyme Sortase A. After the enzymatic reaction takes place in vivo, the history of ligand–receptor interactions is revealed by the presence of reporter tags easily detected by flow cytometry. This proposal aims to determine how interactions between dendritic cells and T cells instruct CD4+ T cells toward distinct fates using LIPSTIC and by implementing other technologies designed ad hoc to measure and understand the biological consequences of relevant cell-cell interactions on T cell fate decision. The combined approaches described here will contribute to the characterization of the molecular signals governing CD4+ T cell response in vivo.
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
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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.
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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.
ERC-STG - Starting Grant
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Call for proposal
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(opens in new window) ERC-2019-STG
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35122 Padova
Italy
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