Revealing dendritic cell-CD4+ T cell communication by using synthetic biology in vivo

Project Information

SYNVIVO

Grant agreement ID: 853179

DOI

10.3030/853179

Project closed

EC signature date 5 November 2019

Start date 1 March 2020

End date 31 August 2025

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 500 000,00

EU contribution

€ 1 500 000,00

Coordinated by

UNIVERSITA DEGLI STUDI DI PADOVA
Italy

Periodic Reporting for period 4 - SYNVIVO (Revealing dendritic cell-CD4+ T cell communication by using synthetic biology in vivo)

Reporting period: 2024-09-01 to 2025-08-31

Summary of the context and overall objectives of the project

T lymphocytes are an essential component of our immune system: they have the power to eradicate infections and tumors, while also ensuring that harmless substances do not trigger unnecessary inflammation. Maintaining this delicate balance requires continuous communication between different types of immune cells. However, current experimental approaches to observe and understand the biological significance of these interactions remain very limited. This project aimed to develop and apply innovative technologies to study cell-to-cell communication in the immune system, so to reveal the cellular and molecular determinants that govern T cell responses. To achieve these aims, we integrated enzymatic intercellular labeling with DNA barcoding, and developed a new technology that allows scientists to identify, pair, and study immune cells that directly interact. We also characterized, at both the cellular and molecular levels, interaction networks that lead to T cell activation or tolerance. Together, these advances have significantly expanded the scientific toolbox for studying immune cell interactions and have provided an unprecedented view of how T cell activation is regulated, offering valuable insights for both fundamental research and biomedical applications. Given the key role of T lymphocytes in infectious diseases, autoimmunity, and cancer, uncovering the factors that control their activity has important implications for developing new vaccines, immunotherapies, and treatments that promote immune balance.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

Since the beginning of the project, we focused our efforts on two main goals: first, to study immune interactions that guide T cell activation and tolerance; and second, to develop a new strategy to monitor cell-to-cell communication which would enable us to univocally identify cells which are part of a same interaction pair. In pursuing the first goal, we analyzed how T cells engage with dendritic cells — specialized immune cells that play a crucial role in activating T cells and shaping immune responses. Our work revealed that different subsets and activation states of dendritic cells can simultaneously support distinct types of T cell responses, highlighting the complexity and precision of immune regulation. For the second goal, we developed an innovative experimental platform in which interacting immune cells are tagged with identical DNA barcodes, allowing researchers to trace and study paired cells at the molecular level. Using this system, we also characterized T cell antigen specificity, opening new possibilities for the analysis of immune specificity. The main results of the project are being disseminated through scientific publications and are also protected by a patent application.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Our work significantly advances the field of immunology by unveiling previously unknown cellular and molecular networks that drive T cell activation. Additionally, our research generated a novel technology that enables scientist to univocally identify cells that are part of an interacting pair, retrieve them and analyze them through sequencing. These biological and methodological advancements have implications for both basic and translational immunology, supporting the development of novel strategies to modulate the immune response and the analysis of immune receptor specificity.

Dendritic cell and T cell interacting in the lymph node