Impact of autophagy on lymphocyte stemness

Efficient immune responses rely on the generation of diversity, represented in T cells by the rise of effector and memory cells. Autophagy is a key mechanism for cellular differentiation, particularly for the establishment of long-term T cell memory. Indeed, upon ageing, when autophagy is impaired, this is accompanied by decreased T cell diversity and inefficient memory responses. Interestingly, asymmetric cell division (ACD), a conserved mechanism that leads to daughter cells inheriting different fate determinants, is also compromised upon ageing. As both autophagy and ACD are required for T cell differentiation, unravelling how they synergistically impact T cell stemness is at the centre of this project. We will investigate (1) how asymmetric autophagy is built, and (2) whether autophagy/ACD loss functionally impacts immune responses by preventing the establishment of asymmetric fates. Our ultimate goal is to understand how autophagy impacts lymphocyte stemness, which may potentially lead to new regenerative medicine strategies.