Rahel Successfully Defends Her Master Thesis!
Rahel Dätwyler has successfully defended her master thesis. You can find her summary below.
Role of TIGIT in limiting immune pathology during RSV infection
Human health is continuously challenged by viruses such as RSV. RSV causes acute respiratory tract infections in infants and is associated with significant morbidity and mortality. Notably, despite intensive research, vaccines and specific treatments against RSV remain unavailable. The immune response mounted against RSV can get out of control and leave behind a lot of damage that potentially increases the risk of developing other types of diseases later in life, for instance autoimmunity and asthma. This is where Treg cells come into play to ensure immune homeostasis. Treg cells are equipped with co-inhibitory receptors including TIGIT that support their role in regulating T cell responses and controlling the balance between allowing for efficient effector functions and restricting tissue damage. TIGIT has recently been linked to limiting immune pathology in an IL-10 dependent manner using the LCMV mouse model. In this thesis, we investigate the impact of TIGIT engagement on tissue integrity and production of the immune modulatory cytokines IL-10, Areg, and TGF-β in a context relevant for human disease. We report that agonistic anti-TIGIT antibody treatment increases the production of IL-10 and Areg by Treg cells during RSV infection. TIGIT ligation leading to upregulation of IL-10 and Areg by Treg cells functionally links TIGIT+ Treg cells to tissue protection during acute viral challenge. We further study the signaling pathway downstream of TIGIT and show that the proteins SRSF6 and RABGEF1 get phosphorylated upon TIGIT ligation. These results bring us one step closer to understanding how the immune system is regulated, which could help in the prospective development of new therapies for guiding excessive immune responses.
