Macroautophagy is an intracellular process of degradation that involves sequestration of cytoplasmic contents into autophagosomes that ultimately fuse with lysosomes for degradation. Our understanding of autophagy has tremendously expanded over the past decade and we have begun to appreciate the considerable potential of modulating autophagy as novel therapeutic strategy in order to treat many pathologies. However, whereas our insight into the mechanistic of this process has increased, evidences are constantly growing and adding complexity and specificity for each tissue and cell type. We and others have demonstrated that autophagy is important for T cell differentiation and function and that autophagy receptors and adaptors play a role in the regulation of T cell responses. We have also shown, that macroautophagy is highly induced upon T cell activation, but its regulation appears to be non-canonical. The molecular mechanisms that control autophagy in T cells are still poorly understood. Our data suggests that the activity of autophagy and the selection of autophagosome cargo in T cells may be regulated differently from other cell types, which may respond to the differential use of specific cargo adaptor proteins. Our goal is, using a recent innovative strategy to screen for protein-protein interactions, to identify autophagy adaptors and receptors that participate in autophagy in T cells and characterized their roles in autophagy and T cell function, We believe that our research will unveil not only new insights into autophagy and T cell biology but will also uncover new intrinsic regulatory mechanisms of autophagy in T cells that may identify potential targets to therapeutically modulate autophagy in T cells in a more specific manner.
Macroautophagy is a process of degradation and recycling of intracellular components. This essential process has been shown to control a wide array of aspects of T cell biology, from activation to survival or differentiation, and therefore, plays a very important role in the regulation of the adaptive immune response. Given the key role of autophagy in many cell and tissues, and the involvement of dysfunctional autophagy in many pathological conditions, intense research has been conducting in understanding how this process is regulated. Our preliminary studies suggest that the regulation of autophagy in T lymphocytes utilizes mechanism that might be specific for this cell type and different from those described for other cell types. In this proposal we aim to identify and characterize those mechanisms with the goal of gaining a better understanding of the roles and regulation of autophagy in the modulation of T cell responses. These findings may help to identify pathways that might be used to specifically target autophagy in T cells with therapeutic purposes.
