Regulation of intestinal T cell homeostasis by autophagy

Mice in which the autophagy protein ATG16L1 was selectively ablated in T cells develop spontaneous intestinal inflammation, characterized by loss of Foxp3+ Treg cells and a selective expansion of Gata3+ Th2 cells. This phenotype was most pronounced in the colonic lamina propria. Thus, a lack of autophagy simultaneously reduces anti-inflammatory Treg cells and increases pro-inflammatory Th2 effector cells in the intestine. This discrepancy could be partly attributed to an altered metabolic programme employed by Atg16l1-deficient Treg cells, with increased glycolysis and impaired fatty acid metabolism. In contrast, the metabolic profile of in vitro polarized Th2 cells seemed to be independent of autophagy. The aims of this thesis are to investigate the mechanistic consequences of altered autophagy in different T cell subsets and also to explore the link between the dominant type 2 immune responses and the observed intestinal pathology.