T Cell Development
Fabio Grassi, Group Leader
Vanessa Cornacchione, Caterina Elisa Faliti, Tanja Rezzonico Jost, Lisa Perruzza, Michele Proietti, Rosita Rigoni, Andrea Romagnani
Adenosine-triphosphate (ATP) is the source of chemical energy for the majority of cellular functions, serves as a substrate in signal transduction pathways and is incorporated into nucleic acids during DNA replication and transcription. ATP can also be released by eukaryotic cells and act as a signalling molecule in an autocrine/paracrine fashion by activating purinergic P2 receptors in the plasma membrane. The research in the lab focuses on the purinergic regulation of T cell physiology, namely T cell receptor (TCR) driven signalling, gene expression and fate determination at various stages of development. Cellular metabolism regulates T cell function and differentiation, and its targeting might be exploited to manipulate adaptive immune responses. T cell stimulation by cognate antigen determines early Ca2+ influx, which cause a burst of oxidative ATP synthesis in the mitochondria. ATP released upon TCR triggering contributes to the activation of mitogen-activated protein kinase (MAPK) through P2X receptors in an autocrine manner. Inhibition of this autocrine purinergic signalling determines T cell anergy and favors polarization of naïve CD4+ cells toward the immunosuppressive regulatory T cell fate. Therefore, pharmacological P2X antagonism might alter adaptive immune system responsiveness. The experiments conducted in the lab are aimed at understanding the role of purinergic signalling in conditioning T cell function in distinct tissue microenvironments.
Projects
- Development of an implantable system to monitor inflammation or metabolism
- Induced thymus development as a therapeutic approach in Omenn Syndrome
- Purinergic regulation of immunosuppressive regulatory T cells
- Regulation of hematopoietic stem cell cycling activity by ATP
- Role of purinergic P2X7 receptor in T cell lineage choice